The aim of the present study was to investigate the anticancer effects and potential mechanisms of polyphenol epigallocatechin-3-gallate (EGCG) on breast cancer MCF-7 cells in vitro and in vivo . Our results showed that EGCG significantly inhibited MCF-7 cell viability in a time- and dose-dependent manner. Flow cytometry analysis indicated that EGCG induced apoptosis and disrupted cell cycle progression at G2/M phase. Moreover, EGCG inhibited miR-25 expression and increased PARP, pro-caspase-3 and pro-caspase-9 at protein levels. Restoration of miR-25 inhibited EGCG-induced cell apoptosis. Furthermore, EGCG suppressed tumor growth in vivo by downregulating the expression of miR-25 and proteins associated with apoptosis, which was further confirmed by a reduction of Ki-67 and increase of pro-apoptotic PARP expression as determined by immunohistochemistry staining. These findings indicate that EGCG possesses chemopreventive potential in breast cancer which may serve as a promising anticancer agent for clinical applications.

autophagy-related 4a (aTG4a) is an autophagy regulator. The current study investigated the role of aTG4a in the development of tamoxifen-resistant breast cancer. aTG4a expression was assessed in tumor and adjacent normal tissue obtained from The cancer Genome atlas database. analyses of the disease-free survival between the aTG4a high and low expression groups was then evaluated in patients with breast cancer. cell viability and apoptosis in McF7/r cells was detected using cell counting Kit-8 assay and flow cytometry, respectively. Gene set enrichment analysis identified the pathway responsible for the effects of aTG4a. The protein expression of aTG4a, lc3, p62, Bcl-2, Bax, GSK-3β, phosphorylated (p)-GSK-3β, β-catenin, cyclind1 and c-myc in McF and McF7/r cells was determined using western blot. in this study, aTG4a expression was increased in the tumor tissues, and a higher aTG4a expression exhibited poor disease-free survival. While 4-hydroxytamoxifen (4-oHT) increased aTG4a expression in McF7 and McF7/r cells, aTG4a expression decreased in the cells treated with 3-methyladenine (3Ma). Treatment with 4-oHT and rapamycin (an autophagy activator) increased the lc3-ii/lc3-i ratio, lc3 puncta number and decreased the level of p62 in McF7/r cells. However, the effects of 4-oHT and rapamycin were reversed by 3Ma and knockdown of aTG4a, respectively. after treatment with 4-oHT, knockdown of aTG4a suppressed proliferation, triggered apoptosis, decreased the expression of Bcl-2, β-catenin, cyclin d1 and c-myc, and increased the expression of Bax and p-GSK3β in McF7/r cells. Moreover, SKl2001, an activator of the Wnt/β-catenin signaling pathway, reversed the effects of aTG4a knockdown on cell viability and apoptosis in McF7/r cells. in conclusion, the knockdown of aTG4a inhibited the anticancer effects of 4-oHT in breast cancer.