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.

• Authors: Yunxin Liu, Weiwei Hua, Yao Li, Xirui Xian, Zheng Zhao, Chao Liu, Jianjun Zou, Jun Li, Xianjun Fang, Yubing Zhu
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 174 Pg. 113776 (04 2020) ISSN: 1873-2968 [Electronic] England
• PMID: 31874145 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2019. Published by Elsevier Inc.

Chemical References

• Antineoplastic Agents, Phytogenic
• Intracellular Signaling Peptides and Proteins
• Membrane Proteins
• SREBF1 protein, human
• SREBP cleavage-activating protein
• Sterol Regulatory Element Binding Protein 1
• Berberine

Topics

• Antineoplastic Agents, Phytogenic (pharmacology, therapeutic use)
• Berberine (pharmacology, therapeutic use)
• Caco-2 Cells
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Colonic Neoplasms (drug therapy, metabolism, pathology)
• Humans
• Intracellular Signaling Peptides and Proteins (metabolism)
• Lipogenesis (drug effects)
• Membrane Proteins (metabolism)
• Signal Transduction
• Sterol Regulatory Element Binding Protein 1 (metabolism)
• Xenograft Model Antitumor Assays