Berberine suppresses colon cancer cell proliferation by inhibiting the SCAP/SREBP-1 signaling pathway-mediated lipogenesis

Abstract

Lipid metabolism is a significant section of energy homeostasis, and it affects the development of various cancers. Previous studies have revealed that berberine has strong anticancer and blood lipid-lowering effects. Here, we further investigated the effects of berberine on cell proliferation and lipogenesis in colon cancer cells and the relationship between the two effects. We found that berberine inhibited cell proliferation by inducing G0/G1 phase cell cycle arrest in colon cancer cells. Moreover, the expressions of key lipogenic enzymes were down-regulated by berberine and led to the suppressed lipid synthesis, which was linked to cell proliferation via Wnt/β-catenin pathway. Importantly, berberine inhibited sterol regulatory element-binding protein-1 (SREBP-1) activation and SREBP cleavage-activating protein (SCAP) expression, resulting in the downregulation of these lipogenic enzymes. Knockdown of SCAP by shRNA could abolish the effect of berberine on SREBP-1 activation. Besides the inhibitory effects in vitro, berberine suppressed the growth and lipogenesis of colon cancer xenograft in a SCAP-dependent manner as well. Together, our results suggest that berberine may serve as a candidate against tumor growth of colon cancer partially through targeting SCAP/SREBP-1 pathway driving lipogenesis.