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Natural Products in Cancer Research: From Isolation to Mechanisms of Action

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

Deadline for manuscript submissions: closed (30 June 2021) | Viewed by 48663

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Special Issue Editor

Dr. Nadine Kretschmer

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Guest Editor

Institute of Pharmaceutical Sciences, Department Pharmacognosy, University of Graz, Universitaetsplatz 4/1, 8010 Graz, Austria
Interests: natural products; cancer research; pharmacological investigations regarding mechanisms of action; activity-guided fractionation and isolation

Special Issue Information

Dear Colleagues,

Despite extensive research, cancer is still the second most common cause of death. The projected increase of cancer incidence from 2018 until 2030 is +62 % according to Cancer Research UK. In 2018, the number of new cases of cancer was around 18 million, with almost 10 million patients dying from this disease. This shows that there is still an urgent need for the development and discovery of novel anti-cancer drugs and treatment options.

This Special Issue welcomes original articles and reviews dealing with the isolation and/or the investigation of mechanisms of action of natural products with potential anti-cancer activity. In vivo studies and the design of novel natural product derivatives with improved efficacy are also welcome. Pharmacological studies should include appropriate positive controls and, if reasonable, non-tumorigenic cells for comparison. Studies that were performed with natural extracts must include a phytochemical characterization of the extracts.

Dr. Nadine Kretschmer
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 submissions that pass pre-check are 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 2700 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

natural products
cancer
cytotoxicity
(activity-guided) isolation of natural products
in vitro studies
in vivo studies

Published Papers (12 papers)

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Research

Jump to: Review

9 pages, 722 KiB

Open AccessArticle

Effects of Curcumin Analogues DMC and EF24 in Combination with the Cytokine TRAIL against Kidney Cancer

by Verónica Ibáñez Gaspar, Jasmin McCaul, Hilary Cassidy, Craig Slattery and Tara McMorrow

Molecules 2021, 26(20), 6302; https://doi.org/10.3390/molecules26206302 - 18 Oct 2021

Cited by 7 | Viewed by 2487

Abstract

The natural compound curcumin has been shown to have therapeutic potential against a wide range of diseases such as cancer. Curcumin reduces cell viability of renal cell carcinoma (RCC) cells when combined with TNF-related apoptosis-inducing ligand (TRAIL), a cytokine that specifically targets cancer cells, by helping overcome TRAIL resistance. However, the therapeutic effects of curcumin are limited by its low bioavailability. Similar compounds to curcumin with higher bioavailability, such as demethoxycurcumin (DMC) and 3,5-bis(2-fluorobenzylidene)-4-piperidone (EF24), can potentially have similar anticancer effects and show a similar synergy with TRAIL, thus reducing RCC viability. This study aims to show the effects of DMC and EF24 in combination with TRAIL at reducing ACHN cell viability and ACHN cell migration. It also shows the changes in death receptor 4 (DR4) expression after treatment with these compounds individually and in combination with TRAIL, which can play a role in their mechanism of action. Full article

(This article belongs to the Special Issue Natural Products in Cancer Research: From Isolation to Mechanisms of Action)

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16 pages, 2121 KiB

Open AccessArticle

Redox Imbalance and Mitochondrial Release of Apoptogenic Factors at the Forefront of the Antitumor Action of Mango Peel Extract

by Valentina Lo Galbo, Marianna Lauricella, Michela Giuliano, Sonia Emanuele, Daniela Carlisi, Giuseppe Calvaruso, Anna De Blasio, Diana Di Liberto and Antonella D’Anneo

Molecules 2021, 26(14), 4328; https://doi.org/10.3390/molecules26144328 - 17 Jul 2021

Cited by 10 | Viewed by 2292

Abstract

Today, an improved understanding of cancer cell response to cellular stress has become more necessary. Indeed, targeting the intracellular pro-oxidant/antioxidant balance triggering the tumor commitment to cell demise could represent an advantageous strategy to develop cancer-tailored therapies. In this scenario, the present study shows how the peel extract of mango—a tropical fruit rich in phytochemicals with nutraceutical properties—can affect the cell viability of three colon cancer cell lines (HT29, Caco-2 and HCT116), inducing an imbalance of cellular redox responses. By using hydro-alcoholic mango peel extract (MPE), we observed a consistent decline in thiol group content, which was accompanied by upregulation of MnSOD—a mitochondrial scavenger enzyme that modulates the cellular response against oxidative damage. Such an effect was the consequence of an early production of mitochondrial superoxide anions that appeared after just 30 min of exposure of colon cancer cells to MPE. The effect was accompanied by mitochondrial injury, consisting of the dissipation of mitochondrial membrane potential and a decrease in the level of proteins localized in the mitochondrial membrane—such as voltage-dependent anion-selective channel (VDAC1), mitofilin, and some members of Bcl-2 family proteins (Mcl-1, Bcl-2 and Bcl-X_L)—with the mitochondrial release of apoptogenic factors (cytochrome C and AIF). The analysis of the cytotoxic effects exerted by the different constituents of MPE (gallic acid, mangiferin, citric acid, quinic acid, pentagalloyl glucose, and methyl gallate) allowed us to identify those phytochemicals responsible for the observed anticancer effects, sustaining their future employment as chemopreventive or therapeutic agents. Full article

(This article belongs to the Special Issue Natural Products in Cancer Research: From Isolation to Mechanisms of Action)

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15 pages, 1237 KiB

Open AccessArticle

Efficacy of a Covalent Microtubule Stabilizer in Taxane-Resistant Ovarian Cancer Models

by Samantha S. Yee and April L. Risinger

Molecules 2021, 26(13), 4077; https://doi.org/10.3390/molecules26134077 - 03 Jul 2021

Cited by 3 | Viewed by 2873

Abstract

Ovarian cancer often has a poor clinical prognosis because of late detection, frequently after metastatic progression, as well as acquired resistance to taxane-based therapy. Herein, we evaluate a novel class of covalent microtubule stabilizers, the C-22,23-epoxytaccalonolides, for their efficacy against taxane-resistant ovarian cancer models in vitro and in vivo. Taccalonolide AF, which covalently binds β-tubulin through its C-22,23-epoxide moiety, demonstrates efficacy against taxane-resistant models and shows superior persistence in clonogenic assays after drug washout due to irreversible target engagement. In vivo, intraperitoneal administration of taccalonolide AF demonstrated efficacy against the taxane-resistant NCI/ADR-RES ovarian cancer model both as a flank xenograft, as well as in a disseminated orthotopic disease model representing localized metastasis. Taccalonolide-treated animals had a significant decrease in micrometastasis of NCI/ADR-RES cells to the spleen, as detected by quantitative RT-PCR, without any evidence of systemic toxicity. Together, these findings demonstrate that taccalonolide AF retains efficacy in taxane-resistant ovarian cancer models in vitro and in vivo and that its irreversible mechanism of microtubule stabilization has the unique potential for intraperitoneal treatment of locally disseminated taxane-resistant disease, which represents a significant unmet clinical need in the treatment of ovarian cancer patients. Full article

(This article belongs to the Special Issue Natural Products in Cancer Research: From Isolation to Mechanisms of Action)

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12 pages, 2347 KiB

Open AccessArticle

Cattleianal and Cattleianone: Two New Meroterpenoids from Psidium cattleianum Leaves and Their Selective Antiproliferative Action against Human Carcinoma Cells

by Engy A. Mahrous, Ahmed M. Al-Abd, Maha M. Salama, Magda M. Fathy, Fathy M. Soliman and Fatema R. Saber

Molecules 2021, 26(10), 2891; https://doi.org/10.3390/molecules26102891 - 13 May 2021

Cited by 5 | Viewed by 2214

Abstract

The Myrteacae family is known as a rich source of phloroglucinols, a group of secondary metabolites with notable biological activities. Leaves of Psidium cattleianum were extracted with chloroform: methanol 8:2 to target the isolation of phloroglucinol derivatives. Isolated compounds were characterized using different spectroscopic methods: nuclear magnetic resonance (NMR), ultra-violet (UV) and mass spectrometry (MS). Two new phloroglucinols were evaluated for cytotoxicity against a panel of six human cancer cell lines, namely colorectal adenocarcinoma cells (HT-29 and HCT-116); hepatocellular carcinoma cells (HepG-2); laryngeal carcinoma (Hep-2); breast adenocarcinoma cells (MCF7 and MDA-MB231), in addition to normal human melanocytes HFB-4. Additionally, cell cycle analysis and annexin-V/FITC-staining were used to gain insights into the mechanism of action of the isolated compounds. The new phloroglucinol meroterpenoids, designated cattleianal and cattleianone, showed selective antiproliferative action against HT-29 cells with IC₅₀’s of 35.2 and 32.1 μM, respectively. Results obtained using cell cycle analysis and annexin-V/FITC-staining implicated both necrosis and apoptosis pathways in the selective cytotoxicity of cattleianal and cattleianone. Our findings suggest that both compounds are selective antiproliferative agents and support further mechanistic studies for phloroglucinol meroterpenoids as scaffolds for developing new selective chemotherapeutic agents. Full article

(This article belongs to the Special Issue Natural Products in Cancer Research: From Isolation to Mechanisms of Action)

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12 pages, 1444 KiB

Open AccessArticle

Cytotoxic Mechanism of Sphaerodactylomelol, an Uncommon Bromoditerpene Isolated from Sphaerococcus coronopifolius

by Celso Alves, Joana Silva, Susete Pinteus, Eva Alonso, Rebeca Alvariño, Adriana Duarte, Diorge Marmitt, Márcia Inês Goettert, Helena Gaspar, Amparo Alfonso, Maria C. Alpoim, Luis M. Botana and Rui Pedrosa

Molecules 2021, 26(5), 1374; https://doi.org/10.3390/molecules26051374 - 04 Mar 2021

Cited by 3 | Viewed by 2524

Abstract

Marine natural products have exhibited uncommon chemical structures with relevant antitumor properties highlighting their potential to inspire the development of new anticancer agents. The goal of this work was to study the antitumor activities of the brominated diterpene sphaerodactylomelol, a rare example of the dactylomelane family. Cytotoxicity (10–100 µM; 24 h) was evaluated on tumor cells (A549, CACO-2, HCT-15, MCF-7, NCI-H226, PC-3, SH-SY5Y, SK-ML-28) and the effects estimated by MTT assay. Hydrogen peroxide (H₂O₂) levels and apoptosis biomarkers (membrane translocation of phosphatidylserine, depolarization of mitochondrial membrane potential, Caspase-9 activity, and DNA condensation and/or fragmentation) were studied in the breast adenocarcinoma cellular model (MCF-7) and its genotoxicity on mouse fibroblasts (L929). Sphaerodactylomelol displayed an IC₅₀ range between 33.04 and 89.41 µM without selective activity for a specific tumor tissue. The cells’ viability decrease was accompanied by an increase on H₂O₂ production, a depolarization of mitochondrial membrane potential and an increase of Caspase-9 activity and DNA fragmentation. However, the DNA damage studies in L929 non-malignant cell line suggested that this compound is not genotoxic for normal fibroblasts. Overall, the results suggest that the cytotoxicity of sphaerodactylomelol seems to be mediated by an increase of H₂O₂ levels and downstream apoptosis. Full article

(This article belongs to the Special Issue Natural Products in Cancer Research: From Isolation to Mechanisms of Action)

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17 pages, 3663 KiB

Open AccessArticle

Suppressing Cdk5 Activity by Luteolin Inhibits MPP⁺-Induced Apoptotic of Neuroblastoma through Erk/Drp1 and Fak/Akt/GSK3β Pathways

by Ratchaneekorn Reudhabibadh, Thunwa Binlateh, Pennapa Chonpathompikunlert, Nongyao Nonpanya, Peerada Prommeenate, Pithi Chanvorachote and Pilaiwanwadee Hutamekalin

Molecules 2021, 26(5), 1307; https://doi.org/10.3390/molecules26051307 - 28 Feb 2021

Cited by 16 | Viewed by 3074

Abstract

Parkinson’s disease (PD) is characterized by the progressive degeneration of dopaminergic neurons. The cause of PD is still unclear. Oxidative stress and mitochondrial dysfunction have been linked to the development of PD. Luteolin, a non-toxic flavonoid, has become interested in an alternative medicine, according to its effects on anti-oxidative stress and anti-apoptosis, although the underlying mechanism of luteolin on PD has not been fully elucidated. This study aims to investigate whether luteolin prevents neurotoxicity induction by 1-methyl-4-phenylpyridinium iodide (MPP⁺), a neurotoxin in neuroblastoma SH-SY5Y cells. The results reveal that luteolin significantly improved cell viability and reduced apoptosis in MPP⁺-treated cells. Increasing lipid peroxidation and superoxide anion (O₂⁻), including mitochondrial membrane potential (Δψm) disruption, is ameliorated by luteolin treatment. In addition, luteolin attenuated MPP⁺-induced neurite damage via GAP43 and synapsin-1. Furthermore, Cdk5 is found to be overactivated and correlated with elevation of cleaved caspase-3 activity in MPP⁺-exposed cells, while phosphorylation of Erk1/2, Drp1, Fak, Akt and GSK3β are inhibited. In contrast, luteolin attenuated Cdk5 overactivation and supported phosphorylated level of Erk1/2, Drp1, Fak, Akt and GSK3β with reducing in cleaved caspase-3 activity. Results indicate that luteolin exerts neuroprotective effects via Cdk5-mediated Erk1/2/Drp1 and Fak/Akt/GSK3β pathways, possibly representing a potential preventive agent for neuronal disorder. Full article

(This article belongs to the Special Issue Natural Products in Cancer Research: From Isolation to Mechanisms of Action)

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10 pages, 1505 KiB

Open AccessCommunication

Polyphyllin D Shows Anticancer Effect through a Selective Inhibition of Src Homology Region 2-Containing Protein Tyrosine Phosphatase-2 (SHP2)

by Se Jeong Kwon, Dohee Ahn, Hyun-Mo Yang, Hyo Jin Kang and Sang J. Chung

Molecules 2021, 26(4), 848; https://doi.org/10.3390/molecules26040848 - 05 Feb 2021

Cited by 7 | Viewed by 3044

Abstract

Natural products have continued to offer tremendous opportunities for drug development, as they have long been used in traditional medicinal systems. SHP2 has served as an anticancer target. To identify novel SHP2 inhibitors with potential anticancer activity, we screened a library containing 658 natural products. Polyphyllin D was found to selectively inhibit SHP2 over SHP1, whereas two other identified compounds (echinocystic acid and oleanolic acid) demonstrated dual SHP1 and SHP2 inhibition. In a cell-based assay, polyphyllin D exhibited cytotoxicity in Jurkat cells, an acute lymphoma leukemia cell line, whereas the other two compounds were ineffective. Polyphyllin D also decreased the level of phosphorylated extracellular signal-regulated kinase (p-ERK), a proliferation marker in Jurkat cells. Furthermore, knockdown of protein tyrosine phosphatase (PTP)N6 (SHP1) or PTPN11 (SHP2) decreased p-ERK levels. However, concurrent knockdown of PTPN6 and PTPN11 in Jurkat cells recovered p-ERK levels. These results demonstrated that polyphyllin D has potential anticancer activity, which can be attributed to its selective inhibition of SHP2 over SHP1. Full article

(This article belongs to the Special Issue Natural Products in Cancer Research: From Isolation to Mechanisms of Action)

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18 pages, 8087 KiB

Open AccessArticle

Ovalitenone Inhibits the Migration of Lung Cancer Cells via the Suppression of AKT/mTOR and Epithelial-to-Mesenchymal Transition

by Kittipong Sanookpan, Nongyao Nonpanya, Boonchoo Sritularak and Pithi Chanvorachote

Molecules 2021, 26(3), 638; https://doi.org/10.3390/molecules26030638 - 26 Jan 2021

Cited by 7 | Viewed by 2825

Abstract

Cancer metastasis is the major cause of about 90% of cancer deaths. As epithelial-to-mesenchymal transition (EMT) is known for potentiating metastasis, this study aimed to elucidate the effect of ovalitenone on the suppression of EMT and metastasis-related behaviors, including cell movement and growth under detached conditions, and cancer stem cells (CSCs), of lung cancer cells. Methods: Cell viability and cell proliferation were determined by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazo-liumbromide (MTT) and colony formation assays. Cell migration and invasion were analyzed using a wound-healing assay and Boyden chamber assay, respectively. Anchorage-independent cell growth was determined. Cell protrusions (filopodia) were detected by phalloidin-rhodamine staining. Cancer stem cell phenotypes were assessed by spheroid formation. The proteins involved in cell migration and EMT were evaluated by Western blot analysis and immunofluorescence staining. Results: Ovalitenone was used at concentrations of 0–200 μM. While it caused no cytotoxic effects on lung cancer H460 and A549 cells, ovalitenone significantly suppressed anchorage-independent growth, CSC-like phenotypes, colony formation, and the ability of the cancer to migrate and invade cells. The anti-migration activity was confirmed by the reduction of filopodia in the cells treated with ovalitenone. Interestingly, we found that ovalitenone could significantly decrease the levels of N-cadherin, snail, and slug, while it increased E-cadherin, indicating EMT suppression. Additionally, the regulatory signaling of focal adhesion kinase (FAK), ATP-dependent tyrosine kinase (AKT), the mammalian target of rapamycin (mTOR), and cell division cycle 42 (Cdc42) was suppressed by ovalitenone. Conclusions: The results suggest that ovalitenone suppresses EMT via suppression of the AKT/mTOR signaling pathway. In addition, ovalitenone exhibited potential for the suppression of CSC phenotypes. These data reveal the anti-metastasis potential of the compound and support the development of ovalitenone treatment for lung cancer therapy. Full article

(This article belongs to the Special Issue Natural Products in Cancer Research: From Isolation to Mechanisms of Action)

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Review

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20 pages, 10119 KiB

Open AccessReview

Chemo-Preventive Action of Resveratrol: Suppression of p53—A Molecular Targeting Approach

by Rokeya Akter, Md. Habibur Rahman, Deepak Kaushik, Vineet Mittal, Diana Uivarosan, Aurelia Cristina Nechifor, Tapan Behl, Chenmala Karthika, Manuela Stoicescu, Mihai Alexandru Munteanu, Cristiana Bustea and Simona Bungau

Molecules 2021, 26(17), 5325; https://doi.org/10.3390/molecules26175325 - 02 Sep 2021

Cited by 19 | Viewed by 3968

Abstract

Extensive experimental, clinical, and epidemiological evidence has explained and proven that products of natural origin are significantly important in preventing and/or ameliorating various disorders, including different types of cancer that researchers are extremely focused on. Among these studies on natural active substances, one can distinguish the emphasis on resveratrol and its properties, especially the potential anticancer role. Resveratrol is a natural product proven for its therapeutic activity, with remarkable anti-inflammatory properties. Various other benefits/actions have also been reported, such as cardioprotective, anti-ageing, antioxidant, etc. and its rapid digestion/absorption as well. This review aims to collect and present the latest published studies on resveratrol and its impact on cancer prevention, molecular signals (especially p53 protein participation), and its therapeutic prospects. The most recent information regarding the healing action of resveratrol is presented and concentrated to create an updated database focused on this topic presented above. Full article

(This article belongs to the Special Issue Natural Products in Cancer Research: From Isolation to Mechanisms of Action)

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21 pages, 30090 KiB

Open AccessReview

Impacting the Remedial Potential of Nano Delivery-Based Flavonoids for Breast Cancer Treatment

by Rakesh K. Sindhu, Rishu Verma, Twinkle Salgotra, Md. Habibur Rahman, Muddaser Shah, Rokeya Akter, Waheed Murad, Sidra Mubin, Parveen Bibi, Safaa Qusti, Eida M. Alshammari, Gaber El-Saber Batiha, Michał Tomczyk and Hayder M. Al-kuraishy

Molecules 2021, 26(17), 5163; https://doi.org/10.3390/molecules26175163 - 26 Aug 2021

Cited by 25 | Viewed by 4699

Abstract

Breast cancer persists as a diffuse source of cancer despite persistent detection and treatment. Flavonoids, a type of polyphenol, appear to be a productive option in the treatment of breast cancer, because of their capacity to regulate the tumor related functions of class of compounds. Plant polyphenols are flavonoids that appear to exhibit properties which are beneficial for breast cancer therapy. Numerous epidemiologic studies have been performed on the dynamic effect of plant polyphenols in the prevention of breast cancer. There are also subclasses of flavonoids that have antioxidant and anticarcinogenic activity. These can regulate the scavenging activity of reactive oxygen species (ROS) which help in cell cycle arrest and suppress the uncontrolled division of cancer cells. Numerous studies have also been performed at the population level, one of which reported a connection between cancer risk and intake of dietary flavonoids. Breast cancer appears to show intertumoral heterogeneity with estrogen receptor positive and negative cells. This review describes breast cancer, its various factors, and the function of flavonoids in the prevention and treatment of breast cancer, namely, how flavonoids and their subtypes are used in treatment. This review proposes that cancer risk can be reduced, and that cancer can be even cured by improving dietary intake. A large number of studies also suggested that the intake of fruit and vegetables is associated with reduced breast cancer and paper also includes the role and the use of nanodelivery of flavonoids in the healing of breast cancer. In addition, the therapeutic potential of orally administered phyto-bioactive compounds (PBCs) is narrowed because of poor stability and oral bioavailability of compounds in the gastrointestinal tract (GIT), and solubility also affects bioavailability. In recent years, creative nanotechnology-based approaches have been advised to enhance the activity of PBCs. Nanotechnology also offers the potential to become aware of disease at earlier stages, such as the detection of hidden or unconcealed metastasis colonies in patients diagnosed with lung, colon, prostate, ovarian, and breast cancer. However, nanoformulation-related effects and safety must not be overlooked. This review gives a brief discussion of nanoformulations and the effect of nanotechnology on herbal drugs. Full article

(This article belongs to the Special Issue Natural Products in Cancer Research: From Isolation to Mechanisms of Action)

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24 pages, 561 KiB

Open AccessReview

Current Status, Distribution, and Future Directions of Natural Products against Colorectal Cancer in Indonesia: A Systematic Review

by Didi Nurhadi Illian, Ihsanul Hafiz, Okpri Meila, Ahmad Rusdan Handoyo Utomo, Arif Nuryawan, Gontar Alamsyah Siregar and Mohammad Basyuni

Molecules 2021, 26(16), 4984; https://doi.org/10.3390/molecules26164984 - 17 Aug 2021

Cited by 4 | Viewed by 2728

Abstract

In 2020, an estimated 19.3 million new cancer cases and nearly 10 million cancer deaths have occurred worldwide, with colorectal cancer ranking as the third most frequently diagnosed (10.0%). Several attempts have been conducted against cancer, including surgery, radiation, monoclonal antibodies, and chemotherapy. Many people choose natural products as alternatives against cancer. These products will not only help in human life preservation but also work as a source of up-to-date information, leading people away from incorrect information. We discuss the current status, distribution, and future implications of protecting populations with natural products as an alternative against colorectal cancer in Indonesia. Thirty-eight studies were included in this review for data extraction. The distribution of natural products in Indonesia that have potential activity against colorectal cancer cells was predominated by terpenoids, followed by phytosterols, phenolics, alkaloids, and polyisoprenoids. The type of cell line utilized in the cytotoxic activity analysis of natural products was the WiDr cell line, followed by HT-29 cells and HCT-116 cells. This review showed that MTT in vitro assay is a general method used to analyze the cytotoxic activity of a natural product against colorectal cancer cells, followed by other in vitro and in vivo methods. The systematic review provided predictions for several secondary metabolites to be utilized as an alternative treatment against colorectal cancer in Indonesia. It also might be a candidate for a future co-chemotherapy agent in safety, quality, and standardization. In addition, computational methods are being developed to predict the drug-likeness of compounds, thus, drug discovery is already on the road towards electronic research and development. Full article

(This article belongs to the Special Issue Natural Products in Cancer Research: From Isolation to Mechanisms of Action)

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27 pages, 1630 KiB

Open AccessReview

Targeting the PI3K/AKT/mTOR Signaling Pathway in Lung Cancer: An Update Regarding Potential Drugs and Natural Products

by Iksen, Sutthaorn Pothongsrisit and Varisa Pongrakhananon

Molecules 2021, 26(13), 4100; https://doi.org/10.3390/molecules26134100 - 05 Jul 2021

Cited by 92 | Viewed by 14241

Abstract

Lung cancer is one of the most common cancers and has a high mortality rate. Due to its high incidence, the clinical management of the disease remains a major challenge. Several reports have documented a relationship between the phosphatidylinositol-3-kinase (PI3K)/ protein kinase B (AKT)/ mammalian target of rapamycin (mTOR) pathway and lung cancer. The recognition of this pathway as a notable therapeutic target in lung cancer is mainly due to its central involvement in the initiation and progression of the disease. Interest in using natural and synthetic medications to target these signaling pathways has increased in recent years, with promising results in vitro, in vivo, and in clinical trials. In this review, we focus on the current understanding of PI3K/AKT/mTOR signaling in tumor development. In addition to the signaling pathway, we highlighted the therapeutic potential of recently developed PI3K/AKT/mTOR inhibitors based on preclinical and clinical trials. Full article

(This article belongs to the Special Issue Natural Products in Cancer Research: From Isolation to Mechanisms of Action)

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