Bound polyphenol from foxtail millet bran exhibits an antiproliferative activity in HT-29 cells by reprogramming miR-149-mediated aerobic glycolysis.

A suggested model for the regulation of aerobic glycolysis in colorectal cancer cells by BPIS. BPIS up-regulated miR-149 level, which lead to the expression inhibition of c-myc. Furthermore, BPIS inhibited c-myc-mediated glycolysis by regulating PKM2 expression and lactate production in colorectal cancer cells. The function of BPIS notably inhibited aerobic glycolysis, which resulted in the decrease of internal ATP levels and an increase in cell death. • BPIS displays an antiproliferative activity in colon cancer cell. • BPIS upregulates miR-149 expression. • C-myc is a new target gene of miR-149. • The effect of BPIS on antiproliferation of colon cancer cells is exerted by reprogramming miR149-mediated aerobic glycolysis. Colorectal cancer (CRC) is an intractable intestinal tumor. Cancer cells prefer to aerobic glycolysis to meet the requirements of rapid proliferation. Hence, discovery of a bioactive molecule cold inhibit aerobic glycolysis, which is regarded as a effective strategies for prevention and treatment of CRC. In this study, we first discovered a foxtail millet bran-derived bound polyphenol (BPIS) with anti-proliferative activity in HT-29 cell (colon cancer cell lines) and its nude mice model. The data further indicated the anti-CRC active ingredients and molecular mechanisms of BPIS. Here we revealed that BPIS could act anti-proliferative activity in HT-29 cells depending on reversing aerobic glycolysis, and this effect was achieved by up-regulation of miR-149 expression by BPIS, which directly targeted the 3′-UTR of c-myc, thereby inhibiting PKM2-mediated aerobic glycolysis. Therefore, BPIS might be used as a new inhibitor of glycolysis for enhancing intestines health benefits. [ABSTRACT FROM AUTHOR]