Shrila Banerjee, Abul Kalam Azad Mandal
Introduction: Breast cancer is a global health concern with increased chemotherapeutic side effects and escalated chemoresistance, requiring alternative therapies. Epigallocatechin-3-gallate (EGCG), a bioactive green tea polyphenol, has exhibited promising anticancer properties. Our study aimed to investigate the tumour-suppressive effect of EGCG and its mechanism in breast cancer. Method: Anticancer activities, such as cell viability, migration, cell cycle progression, and apoptosis, were evaluated. To investigate the molecular mechanism, miR-27a-3p expression was compared against EGCG, a miR-27a-3p inhibitor, and a combination of EGCG with miR-27a-3p inhibitor treatments. The influence of the individual miRNA inhibitor and its combination with EGCG on cell proliferation was also evaluated to establish the anticancer activity of EGCG via miR-27a-3p modulation. The effects of the individual miRNA inhibitor, EGCG, and their combination treatments on key Wnt/β-catenin pathway markers were examined to further establish the therapeutic route of EGCG via the miR-27a/Wnt/β-catenin pathway axis. Result: EGCG notably decreased cell viability and migration, induced apoptosis, and initiated G0/G1 cell cycle arrest. Therapeutic investigation of EGCG on MDA-MB-231 cells indicated its regulatory role on oncogenic miR-27a-3p, which was confirmed when miR-27a-3p expression was significantly lower in the combination treatment of EGCG and the miR-27a-3p inhibitor than in the individual inhibitor treatment in this study. The anticancer potency of the miR-27a-3p inhibitor was also revealed against MDA-MB-231 cells, supporting miRNA therapeutics against cancer. Furthermore, EGCG-modulated miR-27a-3p affected key Wnt/β-catenin pathway markers, causing signal suppression, including suppression of a key Wnt-targeted gene and the G1 phase regulator cyclin-D1, which also indicated its potential against breast cancer. Discussion: These results signify the therapeutic potential of EGCG and its potential implementation through the miR-27a/Wnt/β-catenin pathway axis, resulting in reduced breast cancer proliferation, metastasis, and relapse.