Effect of 6-TG on apoptosis and cell cycle in MCF-7 breast cancer cells and its mechanisms through the regulation of DNMT1

Thioguanine (6-TG) as conventional drug has anti-tumor activity in various cancer cell lines. However, the effect of 6-TG on luminal subtypes breast cancer (ER+, PR+) is elusive. In this study, effect of 6-TG on MCF-7 breast cancer cell line (ER+, PR+) and its mechanisms were investigated. MCF-7 cells were treated with 6-TG and IC50 value was measured by cell counting kit-8 assay. DEGs were confirmed by RNA-seq. Apoptosis and cell cycle consequences were checked by flow cytometry and western blot. Our results showed that colony formation decreased obviously after 6-TG treatment. Moreover, with the treatment of 6-TG cell apoptosis percentage increased. DNMT1 mRNA and protein expression decreased and FAS expression increased in both expression level. Meanwhile, 6-TG treatment also induced MCF-7 cells to occur G2/M phase cell cycle arrest. Overall, our results indicated that 6-TG suppressed cell proliferation, induced G2/M phase arrest through DNMT1 mediated p53-dependent p21 signaling, and accelerated cell apoptosis through activated extrinsic apoptosis pathway which was caused by DNMT1 mediated FAS signaling. Effect of 6-TG on MCF-7 cells.