Background: 6-thioguanine (6-TG), as a conventional “ancient” drug for the treatment of acute leukemia, has been proved to have extensive anti-tumor roles. This study was created to investigate the hidden function of 6-TG on the MCF-7 breast cancer cell line (ER+, PR+) and its mechanisms. Methods: MCF-7 cells were treated with 6-TG, and the IC50 value was measured by a cell counting kit-8 assay. Differentially expressed genes (DEGs) were confirmed by RNA-seq analysis. Apoptosis and cell cycle consequences were determined by flow cytometry and Western blot analyses. Results: The results showed that colony formation decreased markedly and the percentage of cell apoptosis increased after 6-TG treatment. DNMT1 mRNA and protein expression decreased, and FAS expression increased. Moreover, 6-TG also induced MCF-7 cells to undergo G2/M phase cell cycle arrest and upregulated CDKN1A (p21). Conclusion: Overall, our results suggest that 6-TG may induce FAS-mediated exogenous apoptosis and p21-dependent G2/M arrest by inhibiting the activity of DNMT1 in MCF-7 breast cancer cells.
CITATION STYLE
Li, H., An, X., Zhang, D., Li, Q., Zhang, N., Yu, H., & Li, Z. (2020). Transcriptomics analysis of the tumor-inhibitory pathways of 6-thioguanine in MCF-7 cells via silencing dnmt1 activity. OncoTargets and Therapy, 13, 1211–1223. https://doi.org/10.2147/OTT.S236543
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