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Published on: May 24, 2024
Oxyresveratrol Modulates Genes Associated with Apoptosis, Cell Cycle Control and DNA Repair in MCF-7 Cells
Sarayut Radapong1,2, Kelvin Chan2, Satyajit D Sarker2
1Toxicology Laboratory, Medicinal Plant Research Institute, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand.
Abstract:
Oxyresveratrol (OXY) is a small molecule phytochemical which has been reported to have important biological function. The aim of this study was to elucidate the gene expression and biological pathways altered in MCF-7, breast cancer cells following exposure to OXY. The cytotoxicity to different cancer cell lines was screened using MTT assay and then whole gene expression was elucidated using microarray. The pathways selected were also validated by quantitative PCR analysis, fluorometric and western blot assay. A total of 686 genes were found to have altered mRNA expression levels of two-fold or more in the 50 μM OXY-treated group, while 2,338 genes were differentially expressed in the 100 µM-treated group. The relevant visualized global expression patterns of genes and pathways were generated. Apoptosis was activated through mitochondria-lost membrane potential, caspase-3 expression and chromatin condensation without DNA damage. G0/G1 and S phases of the cell cycle control were inhibited dose-dependently by the compound. Rad51 gene (DNA repair pathway) was significantly down-regulated (p < 0.0001). These results indicate that OXY moderates key genes and pathways in MCF-7 cells and that it could be developed as a chemotherapy or chemo-sensitizing agent.
Insights
Oxyresveratrol (OXY) alters gene expression and biological pathways in breast cancer cells. This phytochemical activates apoptosis and inhibits cell cycle progression, suggesting potential as a chemotherapy agent.
Area of Science:
- Molecular Biology
- Cancer Research
- Pharmacology
Background:
- Oxyresveratrol (OXY) is a phytochemical with known biological functions.
- Breast cancer remains a significant global health concern, necessitating novel therapeutic strategies.
Purpose of the Study:
- To investigate the effects of OXY on gene expression and biological pathways in MCF-7 breast cancer cells.
- To evaluate OXY's potential as a chemotherapeutic or chemo-sensitizing agent.
Main Methods:
- Cytotoxicity screening using MTT assay.
- Whole gene expression analysis via microarray.
- Quantitative PCR, fluorometric, and Western blot assays for pathway validation.
Main Results:
- Significant alterations in mRNA expression of 686 genes (50 μM OXY) and 2,338 genes (100 μM OXY).
- OXY activated apoptosis through mitochondrial pathways and caspase-3 expression.
- Dose-dependent inhibition of G0/G1 and S cell cycle phases and significant downregulation of the Rad51 DNA repair gene.
Conclusions:
- OXY modulates key genes and pathways involved in cell death and cell cycle regulation in MCF-7 cells.
- OXY demonstrates potential for development as a novel chemotherapy or chemo-sensitizing agent for breast cancer treatment.
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