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Implication of unfolded protein response in resveratrol-induced inhibition of K562 cell proliferation

Bao-Qin Liu1, Yan-Yan Gao, Xiao-Fang Niu

  • 1Department of Biochemistry & Molecular Biology, China Medical University, Shenyang 110001, China.

Biochemical and Biophysical Research Communications
|December 1, 2009
PubMed

Insights

Resveratrol (RES) halts leukemia cell growth by triggering the unfolded protein response (UPR). This natural compound induces cell cycle arrest, offering potential for new cancer therapies.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Resveratrol (RES), a natural polyphenol, exhibits anti-cancer properties by inducing cell cycle arrest and apoptosis.
  • RES shows promise as a chemopreventive and anti-tumor agent, but its precise mechanisms remain unclear.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying resveratrol's anti-proliferative effects in human leukemia K562 cells.
  • To determine if the unfolded protein response (UPR) is involved in resveratrol-induced cell cycle arrest.

Main Methods:

  • Human leukemia K562 cells were treated with varying concentrations of RES.
  • UPR markers (GRP78, CHOP, eIF2alpha phosphorylation, XBP-1 splicing) were analyzed.
  • Cell cycle progression was assessed using flow cytometry.
  • The role of the PERK/eIF2alpha pathway was evaluated using inhibitors and dominant-negative mutants.

Main Results:

  • RES induced significant cell cycle arrest and inhibited proliferation in K562 cells in a dose-dependent manner.
  • RES treatment led to the induction of key UPR markers, indicating ER stress.
  • RES treatment caused G1 phase cell cycle arrest, which was reversed by inhibiting eIF2alpha or PERK signaling.

Conclusions:

  • Resveratrol induces cell cycle arrest and proliferation inhibition in leukemia cells through the activation of the unfolded protein response (UPR).
  • The PERK/eIF2alpha signaling pathway is crucial for mediating resveratrol's anti-proliferative effects in K562 cells.
  • These findings highlight UPR induction as a potential therapeutic strategy for leukemia treatment using resveratrol.

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