Metformin Reshapes the Methylation Profile in Breast and Colorectal Cancer Cells

Document Type: Research Articles

Authors

1 Department of Genetics, Institute for Research and Medical Consultations, Imam Abdulrahman Bin Faisal University, P. O. Box 1982, Dammam, 31441 Saudi Arabia.

2 College of Biotechnology, Misr University for Science and Technology, Giza, Egypt.

3 Center of Research and Development, Misr University for Science and Technology, Giza, Egypt.

4 Center of Basic Science, Misr University for Science and Technology, Giza, Egypt.

Abstract

With no sharp cure, breast cancer still be the major and the most serious life-threatening disease worldwide. Colorectal
is the third most commonly occurring cancer in men and the second most commonly occurring cancer in women. In the
present investigation, colon cancer cells (CaCo-2) and breast cancer cells (MCF-7) were treated with elevated doses
of metformin (MET) for 48h. Cell count was assessed using trypan blue test, and the cytotoxicity was evaluated using
MTT assay. Methylation-specific PCR was performed on the bisulfite-treated DNA against two tumor suppressor genes;
RASSF1A and RB. Results indicated that: in breast cancer, the cell count was decreased significantly (P>0.005) after
being treated with 5, 10, 20, 50, and 100 mM of MET. The elevated concentration had increased reduction percentages
on the MCF-7 cells, as 5 mM and 100 mM have yielded 35% and 93.3% reduction in cell viability, respectively. Colon
cancer cells have responded to the doses of MET differently, as for the 5 mM and the 100 mM, it gave 88% and 60%
reduction in cells viability, respectively. Cytotoxicity assay revealed that 5 mM and 100 mM of MET caused breast
cancer cells to loss 61.53% and 85.16% of its viability, respectively, whereas colon cancer cells have responded to the
5 mM and 100 mM of MET by reducing the cells viability with 96.91% and 96.24%, respectively. No RB promoter
methylation was detected in colon cells, while RASSF1A was partially methylated. In the MCF-7 breast cancer cells,
both RASSF1A and RB were partially methylated.

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