International Journal of Molecular Sciences

Research

Jump to: Review

14 pages, 926 KiB

Open AccessArticle

Exploring the Therapeutic Potential of trans-Chalcone: Modulation of MicroRNAs Linked to Breast Cancer Progression in MCF-7 Cells

by Tatiana Takahasi Komoto, Felipe Garcia Nishimura, Adriane Feijó Evangelista, Ana Julia Aguiar de Freitas, Gabriel da Silva, Wilson Araujo Silva, Kamila Peronni, Marcia Maria Chiquitelli Marques, Mozart Marins and Ana Lucia Fachin

Int. J. Mol. Sci. 2023, 24(13), 10785; https://doi.org/10.3390/ijms241310785 - 28 Jun 2023

Cited by 1 | Viewed by 1072

Abstract

Breast cancer is responsible for 25% of all cancers that affect women. Due to its high heterogeneity pattern in clinical diagnosis and its molecular profile differences, researchers have been seeking new targets and therapies, with more specificity and fewer side effects. Thus, one [...] Read more.

Breast cancer is responsible for 25% of all cancers that affect women. Due to its high heterogeneity pattern in clinical diagnosis and its molecular profile differences, researchers have been seeking new targets and therapies, with more specificity and fewer side effects. Thus, one compound that has garnered our attention is trans-chalcone, which is naturally occurring in various plants and possesses promising biological properties, including antitumor effects. MiRNA is an extensive class of non-coding small, endogenous, and single-stranded RNAs, and it is involved in post-translational gene regulation. Therefore, the objective of this study was to investigate the effects of TChal on miRNAs expression and its relationship with anticancer activity against MCF-7. Initially, the trans-chalcone IC50 value was established by MTT assay for MCF-7and HaCat (non-cancer cell), in which we found out that it was 53.73 and 44.18

μ

M, respectively. Subsequently, we treated MCF-7 cells with trans-chalcone at its IC50 concentration and performed Mi-seq analysis, which unveiled 23 differentially expressed miRNAs. From this set, we selected five miRNAs (miR-25-5p, miR-27a-3p, miR-891a, miR-449a, and miR-4485) for further validation using qRT-PCR, guided by in silico analysis and their known association with tumorigenesis. In conclusion, our research provides valuable insights into the potential use of TChal to reveal MicroRNAs molecular targets that can be applied in breast cancer therapy. Full article

(This article belongs to the Special Issue Therapeutic Effects of Plant Based Bioactive Compounds on Cancer 2.0)

► Show Figures

Figure 1

12 pages, 2737 KiB

Open AccessArticle

Cytotoxicity Mechanisms of Blue-Light-Activated Curcumin in T98G Cell Line: Inducing Apoptosis through ROS-Dependent Downregulation of MMP Pathways

by Saad Alkahtani, Norah S. AL-Johani, Saud Alarifi and Mohd Afzal

Int. J. Mol. Sci. 2023, 24(4), 3842; https://doi.org/10.3390/ijms24043842 - 14 Feb 2023

Cited by 2 | Viewed by 1636

Abstract

We examined the photodynamic activation of Curcumin under blue light in glioblastoma T98G cells. The therapeutic effect of Curcumin, in both the absence and presence of blue light, was measured by the MTT assay and apoptosis progression using flow cytometry. Fluorescence imaging was [...] Read more.

We examined the photodynamic activation of Curcumin under blue light in glioblastoma T98G cells. The therapeutic effect of Curcumin, in both the absence and presence of blue light, was measured by the MTT assay and apoptosis progression using flow cytometry. Fluorescence imaging was carried out to evaluate Curcumin uptake. Photodynamic activation of Curcumin (10 µM), in the presence of blue light, enhanced its cytotoxic effect, resulting in the activation of ROS-dependent apoptotic pathways in T98G cells. The gene expression studies showed the expression of matrixes metalloproteinase 2 (MMP2) and 9 (MMP9) decrease with Curcumin (10 µM) under blue light exposure, indicating possible proteolytic mechanisms. Moreover, the cytometric appearance displayed that the expressions of NF-κB and Nrf2 were found to be increased upon exposure to blue light, which revealed a significant induction of expression of nuclear factor as a result of blue-light-induced oxidative stress and cell death. These data further demonstrate that Curcumin exhibited a photodynamic effect via induction of ROS-mediated apoptosis in the presence of blue light. Our results suggest that the application of blue light enhances the therapeutic efficacy of Curcumin in glioblastoma because of the phototherapeutic effect. Full article

(This article belongs to the Special Issue Therapeutic Effects of Plant Based Bioactive Compounds on Cancer 2.0)

► Show Figures

Figure 1

16 pages, 1529 KiB

Open AccessArticle

Characterization of the Antitumor Potential of Extracts of Cannabis sativa Strains with High CBD Content in Human Neuroblastoma

by Laura Sánchez-Sánchez, Javier García, Roberto Fernández, Ekaterina Noskova, June Egiguren-Ortiz, Marina Gulak, Eneko Ochoa, Antonio Laso, Mikel Oiarbide, José Ignacio Santos, María Fe Andrés, Azucena González-Coloma, Albert Adell, Egoitz Astigarraga and Gabriel Barreda-Gómez

Int. J. Mol. Sci. 2023, 24(4), 3837; https://doi.org/10.3390/ijms24043837 - 14 Feb 2023

Cited by 2 | Viewed by 2302

Abstract

Cannabis has been used for decades as a palliative therapy in the treatment of cancer. This is because of its beneficial effects on the pain and nausea that patients can experience as a result of chemo/radiotherapy. Tetrahydrocannabinol and cannabidiol are the main compounds [...] Read more.

Cannabis has been used for decades as a palliative therapy in the treatment of cancer. This is because of its beneficial effects on the pain and nausea that patients can experience as a result of chemo/radiotherapy. Tetrahydrocannabinol and cannabidiol are the main compounds present in Cannabis sativa, and both exert their actions through a receptor-mediated mechanism and through a non-receptor-mediated mechanism, which modulates the formation of reactive oxygen species. These oxidative stress conditions might trigger lipidic changes, which would compromise cell membrane stability and viability. In this sense, numerous pieces of evidence describe a potential antitumor effect of cannabinoid compounds in different types of cancer, although controversial results limit their implementation. In order to further investigate the possible mechanism involved in the antitumoral effects of cannabinoids, three extracts isolated from Cannabis sativa strains with high cannabidiol content were analyzed. Cell mortality, cytochrome c oxidase activity and the lipid composition of SH-SY5Y cells were determined in the absence and presence of specific cannabinoid ligands, with and without antioxidant pre-treatment. The cell mortality induced by the extracts in this study appeared to be related to the inhibition of the cytochrome c oxidase activity and to the THC concentration. This effect on cell viability was similar to that observed with the cannabinoid agonist WIN55,212-2. The effect was partially blocked by the selective CB1 antagonist AM281, and the antioxidant α-tocopherol. Moreover, certain membrane lipids were affected by the extracts, which demonstrated the importance of oxidative stress in the potential antitumoral effects of cannabinoids. Full article

(This article belongs to the Special Issue Therapeutic Effects of Plant Based Bioactive Compounds on Cancer 2.0)

► Show Figures

Figure 1

13 pages, 3679 KiB

Open AccessArticle

Effects of Corchorusoside C on NF-κB and PARP-1 Molecular Targets and Toxicity Profile in Zebrafish

by Nathan P. Mirtallo Ezzone, Gerardo D. Anaya-Eugenio, Ermias Mekuria Addo, Yulin Ren, A. Douglas Kinghorn and Esperanza J. Carcache de Blanco

Int. J. Mol. Sci. 2022, 23(23), 14546; https://doi.org/10.3390/ijms232314546 - 22 Nov 2022

Cited by 1 | Viewed by 1252

Abstract

The present study aims to continue the study of corchorusoside C (1), a cardenolide isolated from Streptocaulon juventas, as a potential anticancer agent. A mechanistic study was pursued in a zebrafish model and in DU-145 prostate cancer cells to investigate [...] Read more.

The present study aims to continue the study of corchorusoside C (1), a cardenolide isolated from Streptocaulon juventas, as a potential anticancer agent. A mechanistic study was pursued in a zebrafish model and in DU-145 prostate cancer cells to investigate the selectivity of 1 towards NF-κB and PARP-1 pathway elements. Compound 1 was found to inhibit the expression of IKKα and NF-κB p65 in TNF-α induced zebrafish and inhibit the expression of NIK in vitro. The protein expression levels of XRCC-1 were increased and p53 decreased in DU-145 cells. XIAP protein expression was initially decreased after treatment with 1, followed by an increase in expression at doses higher than the IC₅₀ value. The activity of caspase-1 and the protein expression levels of IL-18 were both decreased following treatment of 1. The binding interactions for 1 to NIK, XRCC-1, p53, XIAP, and caspase-1 proteins were explored in molecular docking studies. Additionally, the toxicity profile of 1 in zebrafish was favorable in comparison to its analog digoxin and other anticancer drugs at the same MTD in zebrafish. Overall, 1 targets the noncanconical NF-κB pathway in vivo and in vitro, and is well tolerated in zebrafish supporting its potential in the treatment of prostate cancer. Full article

(This article belongs to the Special Issue Therapeutic Effects of Plant Based Bioactive Compounds on Cancer 2.0)

► Show Figures

Figure 1

15 pages, 2847 KiB

Open AccessArticle

A Novel Drug Modulator Diarylheptanoid (trans-1,7-Diphenyl-5-hydroxy-1-heptene) from Curcuma comosa Rhizomes for P-glycoprotein Function and Apoptosis Induction in K652/ADR Leukemic Cells

by Natsima Viriyaadhammaa, Suwit Duangmano, Aroonchai Saiai, Montree Tungjai, Pornngarm Dejkriengkraikul, Singkome Tima, Sawitree Chiampanichayakul, Jeffrey Krise and Songyot Anuchapreeda

Int. J. Mol. Sci. 2022, 23(16), 8989; https://doi.org/10.3390/ijms23168989 - 12 Aug 2022

Cited by 1 | Viewed by 1396

Abstract

Curcuma comosa has been used in traditional Thai medicine to treat menstrual cycle-related symptoms in women. This study aims to evaluate the diarylheptanoid drug modulator, trans-1,7-diphenyl-5-hydroxy-1-heptene (DHH), in drug-resistant K562/ADR human leukemic cells. This compound was studied due to its effects [...] Read more.

Curcuma comosa has been used in traditional Thai medicine to treat menstrual cycle-related symptoms in women. This study aims to evaluate the diarylheptanoid drug modulator, trans-1,7-diphenyl-5-hydroxy-1-heptene (DHH), in drug-resistant K562/ADR human leukemic cells. This compound was studied due to its effects on cell cytotoxicity, multidrug resistance (MDR) phenotype, P-glycoprotein (P-gp) expression, and P-gp function. We show that DHH itself is cytotoxic towards K562/ADR cells. However, DHH did not impact P-gp expression. The impact of DHH on the MDR phenotype in the K562/ADR cells was determined by co-treatment of cells with doxorubicin (Dox) and DHH using an MTT assay. The results showed that the DHH changed the MDR phenotype in the K562/ADR cells by decreasing the IC₅₀ of Dox from 51.6 to 18.2 µM. Treating the cells with a nontoxic dose of DHH increased their sensitivity to Dox in P-gp expressing drug-resistant cells. The kinetics of P-gp mediated efflux of pirarubicin (THP) was used to monitor the P-gp function. DHH was shown to suppress THP efflux and resulted in enhanced apoptosis in the K562/ADR cells. These results demonstrate that DHH is a novel drug modulator of P-gp function and induces drug accumulation in the Dox-resistant K562 leukemic cell line. Full article

(This article belongs to the Special Issue Therapeutic Effects of Plant Based Bioactive Compounds on Cancer 2.0)

► Show Figures

Figure 1

Review

Jump to: Research

30 pages, 11214 KiB

Open AccessReview

Salt-Tolerant Plants, Halophytes, as Renewable Natural Resources for Cancer Prevention and Treatment: Roles of Phenolics and Flavonoids in Immunomodulation and Suppression of Oxidative Stress towards Cancer Management

by Hamdoon A. Mohammed, Abdul-Hamid Emwas and Riaz A. Khan

Int. J. Mol. Sci. 2023, 24(6), 5171; https://doi.org/10.3390/ijms24065171 - 08 Mar 2023

Cited by 18 | Viewed by 2343

Abstract

Halophytes and xerophytes, plants with adequate tolerance to high salinity with strong ability to survive in drought ecosystem, have been recognized for their nutritional and medicinal values owing to their comparatively higher productions of secondary metabolites, primarily the phenolics, and the flavonoids, as [...] Read more.

Halophytes and xerophytes, plants with adequate tolerance to high salinity with strong ability to survive in drought ecosystem, have been recognized for their nutritional and medicinal values owing to their comparatively higher productions of secondary metabolites, primarily the phenolics, and the flavonoids, as compared to the normal vegetation in other climatic regions. Given the consistent increases in desertification around the world, which are associated with increasing salinity, high temperature, and water scarcity, the survival of halophytes due to their secondary metabolic contents has prioritized these plant species, which have now become increasingly important for environmental protection, land reclamation, and food and animal-feed security, with their primary utility in traditional societies as sources of drugs. On the medicinal herbs front, because the fight against cancer is still ongoing, there is an urgent need for development of more efficient, safe, and novel chemotherapeutic agents, than those currently available. The current review describes these plants and their secondary-metabolite-based chemical products as promising candidates for developing newer cancer therapeutics. It further discusses the prophylactic roles of these plants, and their constituents in prevention and management of cancers, through an exploration of their phytochemical and pharmacological properties, with a view on immunomodulation. The important roles of various phenolics and structurally diverse flavonoids as major constituents of the halophytes in suppressing oxidative stress, immunomodulation, and anti-cancer effects are the subject matter of this review and these aspects are outlined in details. Full article

(This article belongs to the Special Issue Therapeutic Effects of Plant Based Bioactive Compounds on Cancer 2.0)

► Show Figures

Figure 1

20 pages, 3211 KiB

Open AccessReview

Synthetic Pathways and the Therapeutic Potential of Quercetin and Curcumin

by Aseel Ali Hasan, Victor Tatarskiy and Elena Kalinina

Int. J. Mol. Sci. 2022, 23(22), 14413; https://doi.org/10.3390/ijms232214413 - 20 Nov 2022

Cited by 11 | Viewed by 3554

Abstract

Polyphenols are considered popular ingredients in the pharmaceutical and medical fields due to their preventive and therapeutic properties. However, the potential effects and mechanisms of action of individual polyphenols remain largely unknown. Herein, we analyzed recent data on the synthetic pathways, features, and [...] Read more.

Polyphenols are considered popular ingredients in the pharmaceutical and medical fields due to their preventive and therapeutic properties. However, the potential effects and mechanisms of action of individual polyphenols remain largely unknown. Herein, we analyzed recent data on the synthetic pathways, features, and similarity of the properties of quercetin, as the most famous flavonoid, and curcumin, a representative of curcuminoids that despite their anti-oxidant activity, also have a pro-oxidant effect, depending on the concentration and the cellular environment. This review focuses on an analysis of their anti-cancer efficacy against various cancer cell lines via cell cycle arrest (regulation of p53/p21 and CDK/cyclins) and by triggering the mitochondrial intrinsic (Bcl-2/Bax/caspase 9) apoptotic pathway, as well as through the modulation of the signaling pathways (PI3K/Akt, Wnt/β-catenin, JAK/STAT, MAPK, p53, and NF-ĸB) and their influence on the non-coding RNAs involved in angiogenesis, invasion, migration, and metastasis. The therapeutic potential of quercetin and curcumin is discussed not only on the basis of their anti-cancer effects, but also with regard to their anti-diabetic, anti-obesity, anti-inflammatory, and anti-bacterial actions. Full article

(This article belongs to the Special Issue Therapeutic Effects of Plant Based Bioactive Compounds on Cancer 2.0)

► Show Figures

Figure 1

24 pages, 2230 KiB

Open AccessReview

Flavones: Six Selected Flavones and Their Related Signaling Pathways That Induce Apoptosis in Cancer

by Se Hyo Jeong, Hun Hwan Kim, Sang Eun Ha, Min Young Park, Pritam Bhagwan Bhosale, Abuyaseer Abusaliya, Kwang Il Park, Jeong Doo Heo, Hyun Wook Kim and Gon Sup Kim

Int. J. Mol. Sci. 2022, 23(18), 10965; https://doi.org/10.3390/ijms231810965 - 19 Sep 2022

Cited by 14 | Viewed by 2763

Abstract

Cancer is a horrific disease that, to date, has no cure. It is caused by various factors and takes many lives. Apoptosis is a programmed cell death mechanism and if it does not function correctly in cancer cells, it can lead to severe [...] Read more.

Cancer is a horrific disease that, to date, has no cure. It is caused by various factors and takes many lives. Apoptosis is a programmed cell death mechanism and if it does not function correctly in cancer cells, it can lead to severe disease. There are various signaling pathways for regulating apoptosis in cancer cells. Flavonoids are non-artificial natural bioactive compounds that are gaining attention as being capable of for inducing apoptosis in cancer cells. Among these, in this study, we focus on flavones. Flavones are a subclass of the numerous available flavonoids and possess several bioactive functions. Some of the most reported and well-known critical flavones, namely apigenin, acacetin, baicalein, luteolin, tangeretin, and wogonin, are discussed in depth in this review. Our main aim is to investigate the effects of the selected flavones on apoptosis and cell signaling pathways that contribute to death due to various types of cancers. Full article

(This article belongs to the Special Issue Therapeutic Effects of Plant Based Bioactive Compounds on Cancer 2.0)

► Show Figures