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Special Issue "Antitumoral Properties of Natural Products"

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Natural Products Chemistry".

Deadline for manuscript submissions: 31 October 2019

Special Issue Editor

Guest Editor
Prof. Dr. Roberto Fabiani

Department of Chemistry, Biology and Biotechnology - University of Perugia, Via del Giochetto, 06126 Perugia, Italy
Website | E-Mail
Interests: cancer chemoprevention; nutrition; olive oil; polyphenols; natural bioactive compounds; antioxidants; oxidative stress; genotoxicity; mutagenicity; apoptosis; cell cycle regulation;

Special Issue Information

Cancer is a major public health concern, being one of the main causes of morbidity and mortality worldwide. Carcinogenesis is a complex multistage process in which normal cells trough an alteration of DNA structure/function are transformed into malignant cells acquiring several properties, such as abnormal proliferation and reduced apoptosis. Studies have demonstrated both in vitro and in vivo that many bioactive compounds, from different natural sources, are able to influence a number of pathways related to tumor development. Many different cancer-specific molecular mechanisms and targets have been identified making it possible to use such compounds as alternative therapeutic or adjuvant treatments, or as chemopreventive agents. This Special Issue aims to identify the most recently-discovered new natural bioactive products with anticancer properties and will review their molecular mechanisms of action.

Prof. Dr. Roberto Fabiani
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Cancer
  • Chemoprevention
  • Bioactive compounds
  • Natural products
  • DNA damage
  • Apoptosis
  • Proliferation

Published Papers (26 papers)

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Research

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Open AccessArticle
Effect of Cu/Mn-Fortification on In Vitro Activities of the Peptic Hydrolysate of Bovine Lactoferrin against Human Gastric Cancer BGC-823 Cells
Molecules 2019, 24(7), 1195; https://doi.org/10.3390/molecules24071195
Received: 24 February 2019 / Revised: 22 March 2019 / Accepted: 23 March 2019 / Published: 27 March 2019
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Abstract
Bovine lactoferrin hydrolysate (BLH) was prepared with pepsin, fortified with Cu2+ (Mn2+) 0.64 and 1.28 (0.28 and 0.56) mg/g protein, and then assessed for their activity against human gastric cancer BGC-823 cells. BLH and the four fortified BLH products dose- [...] Read more.
Bovine lactoferrin hydrolysate (BLH) was prepared with pepsin, fortified with Cu2+ (Mn2+) 0.64 and 1.28 (0.28 and 0.56) mg/g protein, and then assessed for their activity against human gastric cancer BGC-823 cells. BLH and the four fortified BLH products dose- and time-dependently had growth inhibition on the cells in both short- and long-time experiments. These samples at dose level of 25 mg/mL could stop cell-cycle progression at the G0/G1-phase, damage mitochondrial membrane, and induce cell apoptosis. In total, the fortified BLH products had higher activities in the cells than BLH alone. Moreover, higher Cu/Mn fortification level brought higher effects, and Mn was more effective than Cu to increase these effects. In the treated cells, the apoptosis-related proteins such as Bad, Bax, p53, cytochrome c, caspase-3, and caspase-9 were up-regulated, while Bcl-2 was down-regulated. Caspase-3 activation was also evidenced using a caspase-3 inhibitor, z-VAD-fmk. Thus, Cu- and especially Mn-fortification of BLH brought health benefits such as increased anti-cancer activity in the BGC-823 cells via activating the apoptosis-related proteins to induce cell apoptosis. Full article
(This article belongs to the Special Issue Antitumoral Properties of Natural Products)
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Open AccessArticle
CLE-10 from Carpesium abrotanoides L. Suppresses the Growth of Human Breast Cancer Cells (MDA-MB-231) In Vitro by Inducing Apoptosis and Pro-Death Autophagy Via the PI3K/Akt/mTOR Signaling Pathway
Molecules 2019, 24(6), 1091; https://doi.org/10.3390/molecules24061091
Received: 22 February 2019 / Revised: 15 March 2019 / Accepted: 16 March 2019 / Published: 20 March 2019
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Abstract
Background: The antitumor activity of CLE-10 (4-epi-isoinuviscolide), a sesquiterpene lactone compound, isolated from Carpesium abrotanoides L. has rarely been reported. The aim of this study is to investigate the antitumor activity of CLE-10 and give a greater explanation of its underlying mechanisms. Methods: [...] Read more.
Background: The antitumor activity of CLE-10 (4-epi-isoinuviscolide), a sesquiterpene lactone compound, isolated from Carpesium abrotanoides L. has rarely been reported. The aim of this study is to investigate the antitumor activity of CLE-10 and give a greater explanation of its underlying mechanisms. Methods: The cytotoxicity of CLE-10 was evaluated using MTT assay. Autophagy was detected by the formation of mRFP-GFP-LC3 fluorescence puncta and observed using transmission electron microscopy, while flow cytometry was employed to detect apoptosis. The protein expressions were detected through Western blotting. Results: CLE-10 induced pro-death autophagy and apoptosis in MDA-MB-231 cells by increasing the protein expression of LC3-II, p-ULK1, Bax, and Bad, as well as downregulating p-PI3K, p-Akt, p-mTOR, p62, LC3-I, Bcl-2, and Bcl-xl. CLE-10 that was pretreated with 3-methyladenine (3-MA) or chloroquine (CQ) weakened the upregulation of the protein expression of p-ULK1, or the downregulation of p62, p-mTOR, and decreased the level of cytotoxicity against MDA-MB-231 cells. Meanwhile, rapamycin enhanced the effect of CLE-10 on the expression of autophagy-related protein and its cytotoxicity, with the IC50 value of CLE-10 decreasing from 4.07 µM to 2.38 µM. Conclusion: CLE-10 induced pro-death autophagy and apoptosis in MDA-MB-231 cells by upregulating the protein expressions of LC3-II, p-ULK1, Bax, and Bad and downregulating p-PI3K, p-Akt, p-mTOR, p62, Bcl-2, and Bcl-xl. Full article
(This article belongs to the Special Issue Antitumoral Properties of Natural Products)
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Open AccessArticle
Antrodin C, an NADPH Dependent Metabolism, Encourages Crosstalk between Autophagy and Apoptosis in Lung Carcinoma Cells by Use of an AMPK Inhibition-Independent Blockade of the Akt/mTOR Pathway
Molecules 2019, 24(5), 993; https://doi.org/10.3390/molecules24050993
Received: 3 February 2019 / Revised: 4 March 2019 / Accepted: 6 March 2019 / Published: 12 March 2019
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Abstract
The current study aims to explore the possible anti-lung carcinoma activity of ADC as well as the underlying mechanisms by which ADC exerts its actions in NSCLC. Findings showed that ADC potently inhibited the viability of SPCA-1, induced apoptosis triggered by ROS, and [...] Read more.
The current study aims to explore the possible anti-lung carcinoma activity of ADC as well as the underlying mechanisms by which ADC exerts its actions in NSCLC. Findings showed that ADC potently inhibited the viability of SPCA-1, induced apoptosis triggered by ROS, and arrested the cell cycle at the G2/M phase via a P53 signaling pathway. Interestingly, phenomena such as autophagosomes accumulation, conversion of the LC3-I to LC3-II, etc., indicated that autophagy could be activated by ADC. The blockage of autophagy-augmented ADC induced inhibition of cell proliferation, while autophagy activation restored cell death, indicating that autophagy had a protective effect against cell death which was induced by ADC treatment. Meanwhile, ADC treatment suppressed both the Akt/mTOR and AMPK signaling pathways. The joint action of both ADC and the autophagy inhibitor significantly increased the death of SPCA-1. An in vitro phase I metabolic stability assay showed that ADC was highly metabolized in SD rat liver microsomes and moderately metabolized in human liver microsomes, which will assist in predicting the outcomes of clinical pharmacokinetics and toxicity studies. These findings imply that blocking the Akt/mTOR signaling pathway, which was independent of AMPK inhibition, could activate ADC-induced protective autophagy in non-small-cell lung cancer cells. Full article
(This article belongs to the Special Issue Antitumoral Properties of Natural Products)
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Open AccessArticle
Bee Venom and Its Peptide Component Melittin Suppress Growth and Migration of Melanoma Cells via Inhibition of PI3K/AKT/mTOR and MAPK Pathways
Molecules 2019, 24(5), 929; https://doi.org/10.3390/molecules24050929
Received: 27 January 2019 / Revised: 28 February 2019 / Accepted: 3 March 2019 / Published: 7 March 2019
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Abstract
Malignant melanoma is the deadliest form of skin cancer and highly chemoresistant. Melittin, an amphiphilic peptide containing 26 amino acid residues, is the major active ingredient from bee venom (BV). Although melittin is known to have several biological activities such as anti-inflammatory, antibacterial [...] Read more.
Malignant melanoma is the deadliest form of skin cancer and highly chemoresistant. Melittin, an amphiphilic peptide containing 26 amino acid residues, is the major active ingredient from bee venom (BV). Although melittin is known to have several biological activities such as anti-inflammatory, antibacterial and anticancer effects, its antimelanoma effect and underlying molecular mechanism have not been fully elucidated. In the current study, we investigated the inhibitory effect and action mechanism of BV and melittin against various melanoma cells including B16F10, A375SM and SK-MEL-28. BV and melittin potently suppressed the growth, clonogenic survival, migration and invasion of melanoma cells. They also reduced the melanin formation in α-melanocyte-stimulating hormone (MSH)-stimulated melanoma cells. Furthermore, BV and melittin induced the apoptosis of melanoma cells by enhancing the activities of caspase-3 and -9. In addition, we demonstrated that the antimelanoma effect of BV and melittin is associated with the downregulation of PI3K/AKT/mTOR and MAPK signaling pathways. We also found that the combination of melittin with the chemotherapeutic agent temozolomide (TMZ) significantly increases the inhibition of growth as well as invasion in melanoma cells compared to melittin or TMZ alone. Taken together, these results suggest that melittin could be potentially applied for the prevention and treatment of malignant melanoma. Full article
(This article belongs to the Special Issue Antitumoral Properties of Natural Products)
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Open AccessArticle
The Extracts of Artemisia absinthium L. Suppress the Growth of Hepatocellular Carcinoma Cells through Induction of Apoptosis via Endoplasmic Reticulum Stress and Mitochondrial-Dependent Pathway
Molecules 2019, 24(5), 913; https://doi.org/10.3390/molecules24050913
Received: 27 January 2019 / Revised: 28 February 2019 / Accepted: 28 February 2019 / Published: 5 March 2019
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Abstract
Artemisia absinthium L. has pharmaceutical and medicinal effects such as antimicrobial, antiparasitic, hepatoprotective, and antioxidant activities. Here, we prepared A. absinthium ethanol extract (AAEE) and its subfractions including petroleum ether (AAEE-Pe) and ethyl acetate (AAEE-Ea) and investigated their antitumor effect on human hepatoma [...] Read more.
Artemisia absinthium L. has pharmaceutical and medicinal effects such as antimicrobial, antiparasitic, hepatoprotective, and antioxidant activities. Here, we prepared A. absinthium ethanol extract (AAEE) and its subfractions including petroleum ether (AAEE-Pe) and ethyl acetate (AAEE-Ea) and investigated their antitumor effect on human hepatoma BEL-7404 cells and mouse hepatoma H22 cells. The cell viability of hepatoma cells was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The apoptosis, cell cycle, mitochondrial membrane potential (Δψm), and reactive oxygen species (ROS) were analyzed by flow cytometry. The levels of proteins in the cell cycle and apoptotic pathways were detected by Western blot. AAEE, AAEE-Pe, and AAEE-Ea exhibited potent cytotoxicity for both BEL-7404 cells and H22 cells through the induction of cell apoptosis and cell cycle arrest. Moreover, AAEE, AAEE-Pe, and AAEE-Ea significantly reduced Δψm, increased the release of cytochrome c, and promoted the cleavage of caspase-3, caspase-9, and poly(ADP-ribose) polymerase (PARP) in BEL-7404 and H22 cells. AAEE, AAEE-Pe, and AAEE-Ea significantly upregulated the levels of ROS and C/EBP-homologous protein (CHOP). Further, AAEE, AAEE-Pe, and AAEE-Ea significantly inhibited tumor growth in the H22 tumor mouse model and improved the survival of tumor mice without side effects. These results suggest that AAEE, AAEE-Pe, and AAEE-Ea inhibited the growth of hepatoma cells through induction of apoptosis, which might be mediated by the endoplasmic reticulum stress and mitochondrial-dependent pathway. Full article
(This article belongs to the Special Issue Antitumoral Properties of Natural Products)
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Open AccessArticle
Cytotoxic Properties of Damiana (Turnera diffusa) Extracts and Constituents and A Validated Quantitative UHPLC-DAD Assay
Molecules 2019, 24(5), 855; https://doi.org/10.3390/molecules24050855
Received: 30 January 2019 / Revised: 21 February 2019 / Accepted: 25 February 2019 / Published: 28 February 2019
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Abstract
In our continuing search for new cytotoxic agents, we assayed extracts, fractions, and pure compounds from damiana (Turnera diffusa) against multiple myeloma (NCI-H929, U266, and MM1S) cell lines. After a first liquid-liquid solvent extraction, the ethyl acetate layer of an acetone [...] Read more.
In our continuing search for new cytotoxic agents, we assayed extracts, fractions, and pure compounds from damiana (Turnera diffusa) against multiple myeloma (NCI-H929, U266, and MM1S) cell lines. After a first liquid-liquid solvent extraction, the ethyl acetate layer of an acetone (70%) crude extract was identified as the most active fraction. Further separation of the active fraction led to the isolation of naringenin (1), three apigenin coumaroyl glucosides 24, and five flavone aglycones 59. Naringenin (1) and apigenin 7-O-(4″-O-p-E-coumaroyl)-glucoside (4) showed significant cytotoxic effects against the tested myeloma cell lines. Additionally, we established a validated ultra-high performance liquid chromatography diode array detector (UHPLC-DAD) method for the quantification of the isolated components in the herb and in traditional preparations of T. diffusa. Full article
(This article belongs to the Special Issue Antitumoral Properties of Natural Products)
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Open AccessArticle
Cucurbitacin B Induces the Lysosomal Degradation of EGFR and Suppresses the CIP2A/PP2A/Akt Signaling Axis in Gefitinib-Resistant Non-Small Cell Lung Cancer
Molecules 2019, 24(3), 647; https://doi.org/10.3390/molecules24030647
Received: 10 December 2018 / Revised: 27 January 2019 / Accepted: 1 February 2019 / Published: 12 February 2019
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Abstract
Non-small cell lung cancer (NSCLC) patients carrying an epidermal growth factor receptor (EGFR) mutation are initially sensitive to EGFR-tyrosine kinase inhibitors (TKIs) treatment, but soon develop an acquired resistance. The treatment effect of EGFR-TKIs-resistant NSCLC patients still faces challenges. Cucurbitacin B (CuB), a [...] Read more.
Non-small cell lung cancer (NSCLC) patients carrying an epidermal growth factor receptor (EGFR) mutation are initially sensitive to EGFR-tyrosine kinase inhibitors (TKIs) treatment, but soon develop an acquired resistance. The treatment effect of EGFR-TKIs-resistant NSCLC patients still faces challenges. Cucurbitacin B (CuB), a triterpene hydrocarbon compound isolated from plants of various families and genera, elicits anticancer effects in a variety of cancer types. However, whether CuB is a viable treatment option for gefitinib-resistant (GR) NSCLC remains unclear. Here, we investigated the anticancer effects and underlying mechanisms of CuB. We report that CuB inhibited the growth and invasion of GR NSCLC cells and induced apoptosis. The inhibitory effect of CuB occurred through its promotion of the lysosomal degradation of EGFR and the downregulation of the cancerous inhibitor of protein phosphatase 2A/protein phosphatase 2A/Akt (CIP2A/PP2A/Akt) signaling axis. CuB and cisplatin synergistically inhibited tumor growth. A xenograft tumor model indicated that CuB inhibited tumor growth in vivo. Immunohistochemistry results further demonstrated that CuB decreased EGFR and CIP2A levels in vivo. These findings suggested that CuB could suppress the growth and invasion of GR NSCLC cells by inducing the lysosomal degradation of EGFR and by downregulating the CIP2A/PP2A/Akt signaling axis. Thus, CuB may be a new drug candidate for the treatment of GR NSCLC. Full article
(This article belongs to the Special Issue Antitumoral Properties of Natural Products)
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Open AccessArticle
Total Phenols from Grape Leaves Counteract Cell Proliferation and Modulate Apoptosis-Related Gene Expression in MCF-7 and HepG2 Human Cancer Cell Lines
Molecules 2019, 24(3), 612; https://doi.org/10.3390/molecules24030612
Received: 18 December 2018 / Revised: 4 February 2019 / Accepted: 5 February 2019 / Published: 10 February 2019
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Abstract
Grape leaves influence several biological activities in the cardiovascular system, acting as antioxidants. In this study, we aimed at evaluating the effect of ethanolic and water extracts from grape leaves grown in Algeria, obtained by accelerator solvent extraction (ASE), on cell proliferation. The [...] Read more.
Grape leaves influence several biological activities in the cardiovascular system, acting as antioxidants. In this study, we aimed at evaluating the effect of ethanolic and water extracts from grape leaves grown in Algeria, obtained by accelerator solvent extraction (ASE), on cell proliferation. The amount of total phenols was determined using the modified Folin-Ciocalteu method, antioxidant activities were evaluated by the 2,2-diphenyl-l-picrylhydrazyl free radical (DPPH*) method and ·OH radical scavenging using electron paramagnetic resonance (EPR) spectroscopy methods. Cell proliferation of HepG2 hepatocarcinoma, MCF-7 human breast cancer cells and vein human umbilical (HUVEC) cells, as control for normal cell growth, was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assay (MTT). Apoptosis- related genes were determined by measuring Bax and Bcl-2 mRNA expression levels. Accelerator solvent extractor yield did not show significant difference between the two solvents (ethanol and water) (p > 0.05). Total phenolic content of water and ethanolic extracts was 55.41 ± 0.11 and 155.73 ± 1.20 mg of gallic acid equivalents/g of dry weight, respectively. Ethanolic extracts showed larger amounts of total phenols as compared to water extracts and interesting antioxidant activity. HepG2 and MCF-7 cell proliferation decreased with increasing concentration of extracts (0.5, 1, and 2 mg/mL) added to the culture during a period of 1–72 h. In addition, the expression of the pro-apoptotic gene Bax was increased and that of the anti-apoptotic gene Bcl-2 was decreased in a dose-dependent manner, when both MCF-7 and HepG2 cells were cultured with one of the two extracts for 72 h. None of the extracts elicited toxic effects on vein umbilical HUVEC cells, highlighting the high specificity of the antiproliferative effect, targeting only cancer cells. Finally, our results suggested that ASE crude extract from grape leaves represents a source of bioactive compounds such as phenols, with potential antioxidants activity, disclosing a novel antiproliferative effect affecting only HepG2 and MCF-7 tumor cells. Full article
(This article belongs to the Special Issue Antitumoral Properties of Natural Products)
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Open AccessArticle
Liposomal Taro Lectin Nanocapsules Control Human Glioblastoma and Mammary Adenocarcinoma Cell Proliferation
Molecules 2019, 24(3), 471; https://doi.org/10.3390/molecules24030471
Received: 22 December 2018 / Revised: 18 January 2019 / Accepted: 23 January 2019 / Published: 29 January 2019
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Abstract
The search for natural anticancer agents and nanocarrier uses are a part of the current strategies to overcome the side effects caused by chemotherapeutics. Liposomal nanocapsules loaded with purified tarin, a potential immunomodulatory and antitumoral lectin found in taro corms, were produced. Liposomes [...] Read more.
The search for natural anticancer agents and nanocarrier uses are a part of the current strategies to overcome the side effects caused by chemotherapeutics. Liposomal nanocapsules loaded with purified tarin, a potential immunomodulatory and antitumoral lectin found in taro corms, were produced. Liposomes were composed by 1,2-dioleoyl-sn-glycerol-3-phosphoethanolamine, cholesterylhemisuccinate, and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[folate(polyethylene glycol)-2000 prepared by thin-film hydration. Small unilamellar vesicles were achieved by sonication and extrusion. Scanning electron microscopy evidenced round-shaped nanocapsules presenting a smooth surface, 150 nm diameter and polydispersity index <0.2, estimated by dynamic light scattering. Tarin entrapment rates were over 80% and leakage of ~3% under 40 days of storage at 4 °C. Entrapped tarin exhibited an 83% release after 6 h at pH 4.6–7.4 and 36 °C. Both free and encapsulated tarin exhibited no in vitro toxicity against healthy mice bone marrow and L929 cells but stimulated the production of fibroblast-like and large round-shaped cells. Encapsulated tarin resulted in inhibition of human glioblastoma (U-87 MG) and breast adenocarcinoma (MDA-MB-231) proliferation, with an IC50 of 39.36 and 71.38 µg/mL, respectively. The effectiveness of encapsulated tarin was similar to conventional chemotherapy drugs, such as cisplatin and temozolide. Tarin liposomal nanocapsules exhibited superior pharmacological activity compared to free tarin as a potential chemotherapy adjuvant. Full article
(This article belongs to the Special Issue Antitumoral Properties of Natural Products)
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Open AccessArticle
Phenolic Compounds of Catalpa speciosa, Taxus cuspidata, and Magnolia acuminata have Antioxidant and Anticancer Activity
Molecules 2019, 24(3), 412; https://doi.org/10.3390/molecules24030412
Received: 6 January 2019 / Revised: 21 January 2019 / Accepted: 22 January 2019 / Published: 23 January 2019
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Abstract
Tree bark represents an important source of medicinal compounds that may be useful for cancer therapy. In the current study, high-performance liquid chromatography with diode-array detection (HPLC-DAD) was used to determine the profile of the phenolic compounds of Catalpa speciosa, Taxus cuspidata [...] Read more.
Tree bark represents an important source of medicinal compounds that may be useful for cancer therapy. In the current study, high-performance liquid chromatography with diode-array detection (HPLC-DAD) was used to determine the profile of the phenolic compounds of Catalpa speciosa, Taxus cuspidata, and Magnolia acuminata bark extracts. The antioxidant and anticancer bioactivities against different cancer cell lines were investigated. M. acuminata exerted significantly higher antioxidant activities in the diphenyl picrylhydrazine and β-carotene-linoleic acid assays than the other species. In C. speciosa, novel profiles of phenolic acids (ferulic acid was the predominant compound) and catechin were detected. In T. cuspidata, six phenolic acids were detected; the predominant compounds were hydroxycaffeic acid and protocatechuic acid. In M. acuminata, two phenolic acids and three catechins were detected; catechin was the predominant compound. The three species exerted clear anticancer activity against MCF-7, HeLa, Jurkat, T24, and HT-29 cells, with the strongest activity found in the extracts from M. acuminata. No antiproliferative activity against normal cells was found. Flow cytometry revealed greater accumulation of necrotic and early/late apoptotic cells in various treated cancer cells than in untreated control cells, and protocatechuic acid induced a similar accumulation of necrotic cells to that of the bark extracts. Caspase-3 and -7 activity was increased in cancer cells treated with different bark extracts; the highest activity was found in the M. acuminata treatment. Our results suggested that the treatment of cancer cells with bark extracts of M. acuminata, C. speciosa, and T. cuspidata, and protocatechuic acid induced apoptosis, suggesting an association between anticancer activities and individual phenolic compounds. Full article
(This article belongs to the Special Issue Antitumoral Properties of Natural Products)
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Open AccessArticle
Evaluating Antitumor and Antioxidant Activities of Yellow Monascus Pigments from Monascus ruber Fermentation
Molecules 2018, 23(12), 3242; https://doi.org/10.3390/molecules23123242
Received: 23 November 2018 / Revised: 4 December 2018 / Accepted: 4 December 2018 / Published: 7 December 2018
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Abstract
Yellow Monascus pigments can be of two kinds: Natural and reduced, in which natural yellow Monascus pigments (NYMPs) attract widespread attention for their bioactivities. In this study, the antioxidative and antibreast cancer effects of the water-soluble NYMPs fermented by Monascus ruber CGMCC 10910 [...] Read more.
Yellow Monascus pigments can be of two kinds: Natural and reduced, in which natural yellow Monascus pigments (NYMPs) attract widespread attention for their bioactivities. In this study, the antioxidative and antibreast cancer effects of the water-soluble NYMPs fermented by Monascus ruber CGMCC 10910 were evaluated. Results showed that water-soluble NYMPs had a significantly improved antioxidative activities compared to the reduced yellow Monascus pigments (RYMPs) that were chemically derived from orange or red Monascus pigments. Furthermore, NYMPs exhibited a concentration-dependent inhibition activity on MCF-7 cell growth (p < 0.001). After a 48-h incubation, a 26.52% inhibition yield was determined with 32 μg/mL of NYMPs. NYMPs also significantly inhibited the migration and invasion of MCF-7 cells. Mechanisms of the activities were associated with a down-regulation of the expression of matrix metalloproteinases and vascular endothelial growth factor. Rather than being alternatively used as natural colorants or antioxidants, this work suggested that NYMPs could be selected as potential functional additives in further test of breast cancer prevention and adjuvant therapy. Full article
(This article belongs to the Special Issue Antitumoral Properties of Natural Products)
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Open AccessArticle
FAK and S6K1 Inhibitor, Neferine, Dually Induces Autophagy and Apoptosis in Human Neuroblastoma Cells
Molecules 2018, 23(12), 3110; https://doi.org/10.3390/molecules23123110
Received: 4 November 2018 / Revised: 24 November 2018 / Accepted: 25 November 2018 / Published: 28 November 2018
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Abstract
Human neuroblastoma cancer is the most typical extracranial solid tumor. Yet, new remedial treatment therapies are demanded to overcome its sluggish survival rate. Neferine, isolated from the lotus embryos, inhibits the proliferation of various cancer cells. This study aimed to evaluate the anti-cancer [...] Read more.
Human neuroblastoma cancer is the most typical extracranial solid tumor. Yet, new remedial treatment therapies are demanded to overcome its sluggish survival rate. Neferine, isolated from the lotus embryos, inhibits the proliferation of various cancer cells. This study aimed to evaluate the anti-cancer activity of neferine in IMR32 human neuroblastoma cells and to expose the concealable molecular mechanisms. IMR32 cells were treated with different concentrations of neferine, followed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to assess cell viability. In an effort to determine the molecular mechanisms in neferine-incubated IMR32 cells, cell cycle arrest, cell migration, and focal adhesion kinase (FAK), the 70-kDa ribosomal S6 kinase 1 (S6K1), poly (ADP-ribose) polymerase (PARP), caspase-3, Beclin-1, and microtubule-associated protein 1A/1B-light chain 3 (LC3) protein expressions were investigated. Neferine strongly disrupted the neuroblastoma cell growth via induction of G2/M phase arrest. Furthermore, neferine provoked autophagy and apoptosis in IMR32 cells, confirmed by p-FAK, and p-S6K1 reduction, LC3-II accumulation, Beclin-1 overexpression, and cleaved caspase-3/PARP improvement. Finally, neferine markedly retarded cell migration of neuroblastoma cancer cells. As a result, our findings for the first time showed an explicit anti-cancer effect of neferine in IMR32 cells, suggesting that neferine might be a potential candidate against human neuroblastoma cells to improve clinical outcomes with further in vivo investigation. Full article
(This article belongs to the Special Issue Antitumoral Properties of Natural Products)
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Open AccessArticle
Tumidulin, a Lichen Secondary Metabolite, Decreases the Stemness Potential of Colorectal Cancer Cells
Molecules 2018, 23(11), 2968; https://doi.org/10.3390/molecules23112968
Received: 9 October 2018 / Revised: 6 November 2018 / Accepted: 12 November 2018 / Published: 14 November 2018
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Abstract
Lichens produce various unique chemicals that are used in the pharmaceutical industry. To screen for novel lichen secondary metabolites that inhibit the stemness potential of colorectal cancer cells, we tested acetone extracts of 11 lichen samples collected in Chile. Tumidulin, isolated from Niebla [...] Read more.
Lichens produce various unique chemicals that are used in the pharmaceutical industry. To screen for novel lichen secondary metabolites that inhibit the stemness potential of colorectal cancer cells, we tested acetone extracts of 11 lichen samples collected in Chile. Tumidulin, isolated from Niebla sp., reduced spheroid formation in CSC221, DLD1, and HT29 cells. In addition, mRNA expressions and protein levels of cancer stem markers aldehyde dehydrogenase-1 (ALDH1), cluster of differentiation 133 (CD133), CD44, Lgr5, and Musashi-1 were reduced after tumidulin treatment. Tumidulin decreased the transcriptional activity of the glioma-associated oncogene homolog zinc finger protein (Gli) promoter in reporter assays, and western blotting confirmed decreased Gli1, Gli2, and Smoothened (SMO) protein levels. Moreover, the tumidulin activity was not observed in the presence of Gli and SMO inhibitors. Together, these results demonstrate for the first time that tumidulin is a potent inhibitor of colorectal cancer cell stemness. Full article
(This article belongs to the Special Issue Antitumoral Properties of Natural Products)
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Open AccessArticle
Quercetagetin and Patuletin: Antiproliferative, Necrotic and Apoptotic Activity in Tumor Cell Lines
Molecules 2018, 23(10), 2579; https://doi.org/10.3390/molecules23102579
Received: 22 August 2018 / Revised: 3 October 2018 / Accepted: 4 October 2018 / Published: 9 October 2018
Cited by 2 | PDF Full-text (10337 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Quercetagetin and patuletin were extracted by the same method from two different Tagetes species that have multiple uses in folk medicine in Mexico and around the globe, one of which is as an anticancer agent. Their biological activity (IC50 and necrotic, apoptotic [...] Read more.
Quercetagetin and patuletin were extracted by the same method from two different Tagetes species that have multiple uses in folk medicine in Mexico and around the globe, one of which is as an anticancer agent. Their biological activity (IC50 and necrotic, apoptotic and selective activities of these flavonols) was evaluated and compared to that of quercetin, examining specifically the effects of C6 substitution among quercetin, quercetagetin and patuletin. We find that the presence of a methoxyl group in C6 enhances their potency. Full article
(This article belongs to the Special Issue Antitumoral Properties of Natural Products)
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Open AccessArticle
Ethylenediamine Derived Carboxamides of Betulinic and Ursolic Acid as Potential Cytotoxic Agents
Molecules 2018, 23(10), 2558; https://doi.org/10.3390/molecules23102558
Received: 11 September 2018 / Revised: 26 September 2018 / Accepted: 3 October 2018 / Published: 8 October 2018
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Abstract
Two easily accessible, natural occurring triterpenoids, betulinic and ursolic acid, were used as starting materials for the synthesis of novel cytotoxic agents. A set of 28 ethylenediamine-spacered carboxamides was prepared holding an additional substituent connected to the ethylenediamine group. The compounds were screened [...] Read more.
Two easily accessible, natural occurring triterpenoids, betulinic and ursolic acid, were used as starting materials for the synthesis of novel cytotoxic agents. A set of 28 ethylenediamine-spacered carboxamides was prepared holding an additional substituent connected to the ethylenediamine group. The compounds were screened in SRB assays to evaluate their cytotoxic activity employing several human tumor cell lines. Betulinic acid-derived carboxamides 1730 showed significantly higher cytotoxicity than their ursolic acid analogs 316. In particular, compounds 25 and 26 were highly cytotoxic, as indicated by EC50 values lower than 1 μM. Full article
(This article belongs to the Special Issue Antitumoral Properties of Natural Products)
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Open AccessArticle
Ganoderma tsugae Inhibits the SREBP-1/AR Axis Leading to Suppression of Cell Growth and Activation of Apoptosis in Prostate Cancer Cells
Molecules 2018, 23(10), 2539; https://doi.org/10.3390/molecules23102539
Received: 12 September 2018 / Revised: 1 October 2018 / Accepted: 3 October 2018 / Published: 5 October 2018
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Abstract
Recent research suggests that the activation of lipid biosynthesis (lipogenesis) is linked with prostate cancer (PCa) malignancy. Sterol regulatory element-binding protein-1 (SREBP-1) is a key transcriptional regulator controlling lipogenesis. Moreover, androgen receptor (AR) has been well defined to play an important role in [...] Read more.
Recent research suggests that the activation of lipid biosynthesis (lipogenesis) is linked with prostate cancer (PCa) malignancy. Sterol regulatory element-binding protein-1 (SREBP-1) is a key transcriptional regulator controlling lipogenesis. Moreover, androgen receptor (AR) has been well defined to play an important role in lethal PCa aggressiveness from androgen-responsive to castration-resistant status. In this study, we showed that the quality-assured Ganoderma tsugae ethanol extract (GTEE), a Chinese natural and herbal product, significantly inhibited expression of SREBP-1 and its downstream genes associated with lipogenesis in PCa cells. Through inhibiting SREBP-1, GTEE reduced the levels of intracellular fatty acids and lipids in PCa cells. Importantly, GTEE also downregulated the expression of AR and prostate-specific antigen (PSA) in both androgen-responsive and castration-resistant PCa cells. By blocking the SREBP-1/AR axis, GTEE suppressed cell growth and progressive behaviors, as well as activating the caspase-dependent apoptotic pathway in PCa cells. These data provide a new molecular basis of GTEE for the development of a potential therapeutic approach to treat PCa malignancy. Full article
(This article belongs to the Special Issue Antitumoral Properties of Natural Products)
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Open AccessArticle
Structural Characterization of Polysaccharides from Dendrobium officinale and Their Effects on Apoptosis of HeLa Cell Line
Molecules 2018, 23(10), 2484; https://doi.org/10.3390/molecules23102484
Received: 4 September 2018 / Revised: 24 September 2018 / Accepted: 25 September 2018 / Published: 27 September 2018
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Abstract
Dendrobium officinale is a widely used medicinal plant in China with numerous bio-activities. However, the main structure and anti-tumor activity of the polysaccharides from this plant have not been investigated. In this study, we elucidated the main structure of polysaccharides purified with DEAE [...] Read more.
Dendrobium officinale is a widely used medicinal plant in China with numerous bio-activities. However, the main structure and anti-tumor activity of the polysaccharides from this plant have not been investigated. In this study, we elucidated the main structure of polysaccharides purified with DEAE and Sephadex G-25 from Dendrobium officinale grown under different planting conditions. In addition, the anti-tumor activity was tested via MTT assays. The results showed that the polysaccharides of Dendrobium officinale grown under different conditions were almost the same, with slight differences in the branched chain; both polysaccharide fractions consisted of (1→4)-linked mannose and (1→4)-linked glucose, with an O-acetyl group in the mannose. After degradation, the polysaccharide fractions from wild plants showed significant anti-proliferation activity in HeLa cells. The fractions F1 and F3 induced apoptosis by up-regulating the expression of ERK, JNK, and p38. We concluded that polysaccharides from Dendrobium officinale planted in the wild exhibit significant anti-tumor effects only after being degraded to smaller molecular weight species. The planting mode is a significant factor in the pharmacological activity of Dendrobium officinale. We advise that the planting conditions for Dendrobium officinale should be changed. Full article
(This article belongs to the Special Issue Antitumoral Properties of Natural Products)
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Open AccessArticle
Microbial Synthesis of Non-Natural Anthraquinone Glucosides Displaying Superior Antiproliferative Properties
Molecules 2018, 23(9), 2171; https://doi.org/10.3390/molecules23092171
Received: 17 July 2018 / Revised: 14 August 2018 / Accepted: 21 August 2018 / Published: 28 August 2018
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Abstract
Anthraquinones, naturally occurring bioactive compounds, have been reported to exhibit various biological activities, including anti-inflammatory, antiviral, antimicrobial, and anticancer effects. In this study, we biotransformed three selected anthraquinones into their novel O-glucoside derivatives, expressing a versatile glycosyltransferase (YjiC) from Bacillus licheniformis DSM [...] Read more.
Anthraquinones, naturally occurring bioactive compounds, have been reported to exhibit various biological activities, including anti-inflammatory, antiviral, antimicrobial, and anticancer effects. In this study, we biotransformed three selected anthraquinones into their novel O-glucoside derivatives, expressing a versatile glycosyltransferase (YjiC) from Bacillus licheniformis DSM 13 in Escherichia coli. Anthraflavic acid, alizarin, and 2-amino-3-hydroxyanthraquinone were exogenously fed to recombinant E. coli as substrate for biotransformation. The products anthraflavic acid-O-glucoside, alizarin 2-O-β-d-glucoside, and 2-amino-3-O-glucosyl anthraquinone produced in the culture broths were characterized by various chromatographic and spectroscopic analyses. The comparative anti-proliferative assay against various cancer cells (gastric cancer-AGS, uterine cervical cancer-HeLa, and liver cancer-HepG2) were remarkable, since the synthesized glucoside compounds showed more than 60% of cell growth inhibition at concentrations ranging from ~50 μM to 100 μM. Importantly, one of the synthesized glucoside derivatives, alizarin 2-O-glucoside inhibited more than 90% of cell growth in all the cancer cell lines tested. Full article
(This article belongs to the Special Issue Antitumoral Properties of Natural Products)
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Open AccessArticle
Zeylenone Induces Mitochondrial Apoptosis and Inhibits Migration and Invasion in Gastric Cancer
Molecules 2018, 23(9), 2149; https://doi.org/10.3390/molecules23092149
Received: 8 August 2018 / Revised: 20 August 2018 / Accepted: 23 August 2018 / Published: 27 August 2018
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Abstract
The mortality of gastric cancer (GC) is increasing due to its high rates of recurrence and metastasis. Zeylenone (Zey), a type of naturally occurring cyclohexene oxide, was demonstrated to be effective in cancer patients. The aim of this study is to explore the [...] Read more.
The mortality of gastric cancer (GC) is increasing due to its high rates of recurrence and metastasis. Zeylenone (Zey), a type of naturally occurring cyclohexene oxide, was demonstrated to be effective in cancer patients. The aim of this study is to explore the anti-cancer effect of Zey against gastric cancer both in vitro and in vivo, as well as the underlying mechanisms. We found that Zey inhibited gastric tumor growth, as demonstrated by in vitro gastric cancer cell lines and in a human gastric cancer xenograft mouse model. Furthermore, Zey induced substantial apoptosis through a mitochondrial apoptotic pathway, involving mitochondrial transmembrane potential loss, caspase-3 activation, anti-apoptotic protein downregulation, and pro-apoptotic protein upregulation. Notably, we revealed for the first time that Zey suppressed invasion and migration by wound healing and transwell chamber assays. Through Western blotting, we further explored the potential mechanism of Zey’s anti-cancer activity. We found that Zey downregulated the expression of matrix metalloproteinase 2/9 (MMP 2/9) and inhibited the phosphorylation of AKT and ERK. In short, Zey, which induced mitochondrial apoptosis and inhibited proliferation, migration, and invasion, may be developed as a novel drug for the treatment of gastric cancer. Full article
(This article belongs to the Special Issue Antitumoral Properties of Natural Products)
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Open AccessArticle
JNK Inactivation Induces Polyploidy and Drug-Resistance in Coronarin D-Treated Osteosarcoma Cells
Molecules 2018, 23(9), 2121; https://doi.org/10.3390/molecules23092121
Received: 27 July 2018 / Revised: 19 August 2018 / Accepted: 21 August 2018 / Published: 23 August 2018
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Abstract
Inhibition of proliferating cells is a critical strategy for cancer therapy. In this study, we demonstrated that coronarin D, a natural component extracted from the rhizomes of Hedychium coronarium, significantly suppressed the proliferation of osteosarcoma cells. The treatment with coronarin D resulted [...] Read more.
Inhibition of proliferating cells is a critical strategy for cancer therapy. In this study, we demonstrated that coronarin D, a natural component extracted from the rhizomes of Hedychium coronarium, significantly suppressed the proliferation of osteosarcoma cells. The treatment with coronarin D resulted in the activation of caspase-3 and apoptosis. This treatment induced the accumulation of cyclin B1 and DNA condensation indicating the treated osteosarcoma cells were arrested in mitotic phase. Furthermore, the treatment with coronarin D increased the levels of phosphorylated c-Jun NH2-terminal kinase (JNK) in human osteosarcoma cells. Pretreatment with JNK inhibitor blocked the accumulation of cyclin B1 and DNA condensation, resulting the accumulation of tetraploid cells in coronarin D-treated osteosarcoma HOS cells, indicating JNK inactivation blocked the mitotic entry and arrested cells in the 4 N state. After adaptation, the arrested tetraploid cells continued to duplicate their DNA resulting in polyploidy. Interestingly, when the arrested mitotic cells induced by coronarin D were treated with JNK inhibitor, the accumulated cyclin B1 and DNA condensation were immediately eliminated. These arrested 4 N cells loss the ability to undergo cytokinesis, and ultimately continued to duplicate DNA upon prolonged arrest resulting in the production of polyploid populations. JNK inactivation, either by the pretreatment with JNK inhibitor or the treatment with JNK inhibitor in coronarin D-induced mitotic cells, both caused resistance to coronarin D-induced cell death. Taken together, our findings indicate that coronarin D induces the apoptosis and mitosis arrest in human osteosarcoma cells. JNK has a crucial role in coronarin D-induced mitosis arrest and apoptosis. We hypothesize that functional evaluation of JNK may produce more specific and effective therapies in coronarin D-related trail for treatment of human osteosarcoma. Full article
(This article belongs to the Special Issue Antitumoral Properties of Natural Products)
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Open AccessArticle
Novel Polyketides Produced by the Endophytic Fungus Aspergillus Fumigatus from Cordyceps Sinensis
Molecules 2018, 23(7), 1709; https://doi.org/10.3390/molecules23071709
Received: 21 June 2018 / Revised: 6 July 2018 / Accepted: 7 July 2018 / Published: 13 July 2018
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Abstract
Five new polyketides, including two pairs of enantiomers and a racemate, were isolated from the fermentation broth of Aspergillus fumigatus, an endophytic fungus isolated from Cordyceps sinensis. Their structures were identified using one-dimensional (1D) and two-dimensional (2D) NMR experiments, and the [...] Read more.
Five new polyketides, including two pairs of enantiomers and a racemate, were isolated from the fermentation broth of Aspergillus fumigatus, an endophytic fungus isolated from Cordyceps sinensis. Their structures were identified using one-dimensional (1D) and two-dimensional (2D) NMR experiments, and the absolute configurations of the enantiomers were confirmed using electronic circular dichroism (ECD) calculations. Compounds 1a and 2a exhibited inhibitory activity against the MV4-11 cell line in vitro, with IC50 values of 23.95 µM and 32.70 µM, respectively. Full article
(This article belongs to the Special Issue Antitumoral Properties of Natural Products)
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Open AccessFeature PaperArticle
Cytotoxic Triterpenes from Salacia crassifolia and Metabolite Profiling of Celastraceae Species
Molecules 2018, 23(6), 1494; https://doi.org/10.3390/molecules23061494
Received: 2 June 2018 / Revised: 15 June 2018 / Accepted: 18 June 2018 / Published: 20 June 2018
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Abstract
The new pentacyclic triterpene 11β-hydroxypristimerin (1), along with the known metabolites pristimerin (2), 6-oxopristimerol (3) and vitideasin (4), were isolated from a Salacia crassifolia root wood extract, following a bioassay-guided fractionation approach. Both [...] Read more.
The new pentacyclic triterpene 11β-hydroxypristimerin (1), along with the known metabolites pristimerin (2), 6-oxopristimerol (3) and vitideasin (4), were isolated from a Salacia crassifolia root wood extract, following a bioassay-guided fractionation approach. Both the extract and the purified triterpenes displayed pronounced cytotoxic activity against human cancer cell lines. The NCI-60 cell line screen revealed that compound 2 was the most active, with a mean GI50 of 0.17 μM, while compound 1 had a mean GI50 of 8.7 μM. A COMPARE analysis of the screening results showed that pristimerin is likely to be the main compound responsible for the cytotoxic activity of the extract (mean GI50 of 0.3 μg·mL−1). A targeted search for pristimerin and related derivatives using LC-MS/MS revealed the presence of pristimerin (2) and 6-oxopristimerol (3) in all Celastraceae species examined and in all plant parts tested, while vitideasin (4) was only detected in the genus Salacia. Full article
(This article belongs to the Special Issue Antitumoral Properties of Natural Products)
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Review

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Open AccessReview
Pleiotropic Pharmacological Actions of Capsazepine, a Synthetic Analogue of Capsaicin, against Various Cancers and Inflammatory Diseases
Molecules 2019, 24(5), 995; https://doi.org/10.3390/molecules24050995
Received: 18 February 2019 / Revised: 7 March 2019 / Accepted: 8 March 2019 / Published: 12 March 2019
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Abstract
Capsazepine is a synthetic analogue of capsaicin that can function as an antagonist of TRPV1. Capsazepine can exhibit diverse effects on cancer (prostate cancer, breast cancer, colorectal cancer, oral cancer, and osteosarcoma) growth and survival, and can be therapeutically used against other major [...] Read more.
Capsazepine is a synthetic analogue of capsaicin that can function as an antagonist of TRPV1. Capsazepine can exhibit diverse effects on cancer (prostate cancer, breast cancer, colorectal cancer, oral cancer, and osteosarcoma) growth and survival, and can be therapeutically used against other major disorders such as colitis, pancreatitis, malaria, and epilepsy. Capsazepine has been reported to exhibit pleiotropic anti-cancer effects against numerous tumor cell lines. Capsazepine can modulate Janus activated kinase (JAK)/signal transducer and activator of the transcription (STAT) pathway, intracellular Ca2+ concentration, and reactive oxygen species (ROS)-JNK-CCAAT/enhancer-binding protein homologous protein (CHOP) pathways. It can inhibit cell proliferation, metastasis, and induce apoptosis. Moreover, capsazepine can exert anti-inflammatory effects through the downregulation of lipopolysaccharide (LPS)-induced nuclear transcription factor-kappa B (NF-κB), as well as the blockage of activation of both transient receptor potential cation channel subfamily V member 1 (TRPV1) and transient receptor potential cation channel, subfamily A, and member 1 (TRPA1). This review briefly summarizes the diverse pharmacological actions of capsazepine against various cancers and inflammatory conditions. Full article
(This article belongs to the Special Issue Antitumoral Properties of Natural Products)
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Open AccessReview
Dietary Phytochemicals Targeting Cancer Stem Cells
Molecules 2019, 24(5), 899; https://doi.org/10.3390/molecules24050899
Received: 8 February 2019 / Revised: 25 February 2019 / Accepted: 28 February 2019 / Published: 4 March 2019
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Abstract
There is an increasing awareness of the importance of a diet rich in fruits and vegetables for human health. Cancer stem cells (CSCs) are characterized as a subpopulation of cancer cells with aberrant regulation of self-renewal, proliferation or apoptosis leading to cancer progression, [...] Read more.
There is an increasing awareness of the importance of a diet rich in fruits and vegetables for human health. Cancer stem cells (CSCs) are characterized as a subpopulation of cancer cells with aberrant regulation of self-renewal, proliferation or apoptosis leading to cancer progression, invasiveness, metastasis formation, and therapy resistance. Anticancer effects of phytochemicals are also directed to target CSCs. Here we provide a comprehensive review of dietary phytochemicals targeting CSCs. Moreover, we evaluate and summarize studies dealing with effects of dietary phytochemicals on CSCs of various malignancies in preclinical and clinical research. Dietary phytochemicals have a significant impact on CSCs which may be applied in cancer prevention and treatment. However, anticancer effects of plant derived compounds have not yet been fully investigated in clinical research. Full article
(This article belongs to the Special Issue Antitumoral Properties of Natural Products)
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Open AccessFeature PaperReview
Potential of Zerumbone as an Anti-Cancer Agent
Molecules 2019, 24(4), 734; https://doi.org/10.3390/molecules24040734
Received: 21 December 2018 / Revised: 15 February 2019 / Accepted: 16 February 2019 / Published: 18 February 2019
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Abstract
Cancer is still a major risk factor to public health globally, causing approximately 9.8 million deaths worldwide in 2018. Despite advances in conventional treatment modalities for cancer treatment, there are still few effective therapies available due to the lack of selectivity, adverse side [...] Read more.
Cancer is still a major risk factor to public health globally, causing approximately 9.8 million deaths worldwide in 2018. Despite advances in conventional treatment modalities for cancer treatment, there are still few effective therapies available due to the lack of selectivity, adverse side effects, non-specific toxicities, and tumour recurrence. Therefore, there is an immediate need for essential alternative therapeutics, which can prove to be beneficial and safe against cancer. Various phytochemicals from natural sources have been found to exhibit beneficial medicinal properties against various human diseases. Zerumbone is one such compound isolated from Zingiber zerumbet Smith that possesses diverse pharmacological properties including those of antioxidant, antibacterial, antipyretic, anti-inflammatory, immunomodulatory, as well as anti-neoplastic. Zerumbone has shown its anti-cancer effects by causing significant suppression of proliferation, survival, angiogenesis, invasion, and metastasis through the molecular modulation of different pathways such as NF-κB, Akt, and IL-6/JAK2/STAT3 (interleukin-6/janus kinase-2/signal transducer and activator of transcription 3) and their downstream target proteins. The current review briefly summarizes the modes of action and therapeutic potential of zerumbone against various cancers. Full article
(This article belongs to the Special Issue Antitumoral Properties of Natural Products)
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Open AccessReview
Biochemical Basis of Anti-Cancer-Effects of Phloretin—A Natural Dihydrochalcone
Molecules 2019, 24(2), 278; https://doi.org/10.3390/molecules24020278
Received: 24 December 2018 / Revised: 8 January 2019 / Accepted: 10 January 2019 / Published: 13 January 2019
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Abstract
Apple is a rich source of bioactive phytochemicals that help improve health by preventing and/or curing many disease processes, including cancer. One of the apple polyphenols is phloretin [2′,4′,6′-Trihydroxy-3-(4-hydroxyphenyl)-propiophenone], which has been widely investigated for its antioxidant, anti-inflammatory and anti-cancer activities in a [...] Read more.
Apple is a rich source of bioactive phytochemicals that help improve health by preventing and/or curing many disease processes, including cancer. One of the apple polyphenols is phloretin [2′,4′,6′-Trihydroxy-3-(4-hydroxyphenyl)-propiophenone], which has been widely investigated for its antioxidant, anti-inflammatory and anti-cancer activities in a wide array of preclinical studies. The efficacy of phloretin in suppressing xenograft tumor growth in athymic nude mice implanted with a variety of human cancer cells, and the ability of the compound to interfere with cancer cells signaling, have made it a promising candidate for anti-cancer drug development. Mechanistically, phloretin has been reported to arrest the growth of tumor cells by blocking cyclins and cyclin-dependent kinases and induce apoptosis by activating mitochondria-mediated cell death. The blockade of the glycolytic pathway via downregulation of GLUT2 mRNA and proteins, and the inhibition of tumor cells migration, also corroborates the anti-cancer effects of phloretin. This review sheds light on the molecular targets of phloretin as a potential anti-cancer and anti-inflammatory natural agent. Full article
(This article belongs to the Special Issue Antitumoral Properties of Natural Products)
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