Cell cycle and apoptosis pathway modulation by Tualang honey in ER-dependent and -independent breast cancer cell lines

Abstract

We previously demonstrated that Tualang honey (TH) induced apoptosis in breast cancer cell lines, via activation of caspase-3/7, -8, and -9 and mitochondrial membrane depolarization. Here we investigated the effect of TH on cell cycle progression and its regulatory molecules as well as apoptosis-related signaling molecules in estrogen receptor-dependent MCF-7 and -independent breast MDA-MB-231 cancer cells. Flow cytometry analysis shows that 24 h treatment with 1% TH caused G2/M phase arrest in MCF-7 but S phase arrest in MDA-MB-231 cells. Significant changes in the expression of apoptosis-related genes were observed in MCF-7 cells but not in MDA-MB-231 cells. We further demonstrated by Western blotting that TH increased the expression of p53, p21, and FADD proteins in MCF-7 cells and TRADD, FADD, and p21 proteins in MDA-MB-231 cells. This study shows that TH differentially affects the cell cycle progression of MCF-7 and MDA-MB-231 cells via p53-dependent and -independent p21 signaling, respectively, and apoptosis via the death receptor pathway is indicated. Taken together, the ability of TH to modulate cell signaling pathways suggest the potential value of a readily consumed honey as a chemopreventive agent for breast cancer.