Berberine inhibits proliferation and induces G0/G1 phase arrest in colorectal cancer cells by downregulating IGF2BP3

Life Sci. 2020 Nov 1:260:118413. doi: 10.1016/j.lfs.2020.118413. Epub 2020 Sep 11.

Abstract

Aims: Berberine (BBR) is one of isoquinoline alkaloids from Coptidis Rhizoma and possesses extensive pharmacological activities, including anti-colorectal cancer (CRC) activity. However, the detailed mechanisms remain to be determined. The current study aims to investigate the ability and the potential mechanism of BBR against CRC.

Main methods: By mining recognized CRC datasets and RNA-seq results of cells and tumors treated with BBR for perform bioinformatics analysis to find key targets IGF2BP3. Overexpression and knockdown of IGF2BP3 assays were used to explore the biological role of IGF2BP3 in the process of BBR against CRC.

Key findings: Our results showed that BBR inhibits proliferation and induces G0/G1 phase arrest in CRC cells by downregulating IGF2BP3. Specifically, Knockdown of IGF2BP3 could suppress the PI3K/AKT pathway to inhibit cell proliferation and cycle transition. The negative effects of BBR in CRC cells could be rescued by overexpressing IGF2BP3.

Significance: Our data might provide a theoretical basis for the future use of BBR in colorectal cancer prevention.

Keywords: Berberine (BBR); Colorectal cancer (CRC); IGF2BP3; PI3K/AKT.

MeSH terms

  • Animals
  • Apoptosis
  • Berberine / pharmacology*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Cell Proliferation
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology*
  • Female
  • G1 Phase / drug effects*
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • RNA-Binding Proteins / antagonists & inhibitors*
  • RNA-Binding Proteins / metabolism
  • Resting Phase, Cell Cycle / drug effects*
  • Signal Transduction
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • IGF2BP3 protein, human
  • RNA-Binding Proteins
  • Berberine