Transcriptomics Analysis of the Tumor-Inhibitory Pathways of 6-Thioguanine in MCF-7 Cells via Silencing DNMT1 Activity.

Abstract

Background6-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.MethodsMCF-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.ResultsThe 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).ConclusionOverall, 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.