Berberine enhances chemosensitivity to irinotecan in colon cancer via inhibition of NF‑κB

Mol Med Rep. 2014 Jan;9(1):249-54. doi: 10.3892/mmr.2013.1762. Epub 2013 Oct 29.

Abstract

Previous studies have shown that irinotecan (CPT‑11) impairs chemotherapy‑induced apoptosis by activating nuclear factor‑κB (NF‑κB) and a number of strategies have been employed to augment chemosensitivity through the suppression of NF‑κB activation. Berberine, a botanical alkaloid, was reported to enhance chemosensitivity to 5‑fluorouracil and doxorubicin by suppressing NF‑κB activation. In the present study, the effect of berberine on CPT‑11‑induced apoptosis was investigated through the inhibition of NF‑κB. Inhibition of NF‑κB activation by p65 small interfering RNA was shown to potentiate apoptosis induced by CPT‑11. Berberine suppressed CPT‑11‑induced NF‑κB activation in a dose‑dependent manner and enhanced chemosensitivity to CPT‑11 by downregulating NF‑κB activation of antiapoptotic genes, c‑IAP1, c‑IAP2, survivin and Bcl‑xL. The current observations indicate that berberine inhibits NF‑κB activation and may be used to enhance CPT‑11‑induced apoptosis in colon cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / metabolism
  • Berberine / pharmacology*
  • Camptothecin / analogs & derivatives*
  • Camptothecin / pharmacology
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Down-Regulation / drug effects
  • Doxorubicin / pharmacology
  • Fluorouracil / pharmacology
  • HCT116 Cells
  • Humans
  • Inhibitor of Apoptosis Proteins / metabolism
  • Irinotecan
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism*
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Survivin
  • Transcription Factor RelA / antagonists & inhibitors
  • Transcription Factor RelA / genetics
  • Transcription Factor RelA / metabolism
  • bcl-X Protein / metabolism

Substances

  • Antineoplastic Agents
  • Apoptosis Regulatory Proteins
  • BIRC5 protein, human
  • Inhibitor of Apoptosis Proteins
  • NF-kappa B
  • RNA, Small Interfering
  • Survivin
  • Transcription Factor RelA
  • bcl-X Protein
  • Berberine
  • Irinotecan
  • Doxorubicin
  • Fluorouracil
  • Camptothecin