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Updated: Jul 5, 2026

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

Involvement of PI3K/AKT/GSK3beta pathway in tetrandrine-induced G1 arrest and apoptosis

Xuan-li Chen1, Kai-huan Ren, Hong-wei He

  • 1Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

Cancer Biology & Therapy
|April 26, 2008
PubMed

Insights

Tetrandrine triggers cancer cell death by halting the cell cycle and inducing apoptosis. This study reveals the phosphoinositide 3-kinase/AKT/glycogen synthase kinase-3 beta (PI3K/AKT/GSK3β) pathway is crucial for these effects.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Tetrandrine is known to induce cell cycle arrest and apoptosis in human cancer cells.
  • The PI3K/AKT/GSK3β signaling pathway plays a critical role in cell proliferation, survival, and apoptosis.

Purpose of the Study:

  • To investigate the role of the PI3K/AKT/GSK3β pathway in tetrandrine-induced G1 arrest and apoptosis.
  • To elucidate the molecular mechanisms underlying tetrandrine's anti-cancer effects.

Main Methods:

  • Utilized HT-29 human colon cancer cells.
  • Analyzed protein expression and phosphorylation levels (AKT, GSK3β, p27kip1, cyclin D1).
  • Assessed apoptosis markers (caspase 3, PARP cleavage) and cell cycle progression.
  • Employed selective GSK3β inhibitors and small interfering RNA (siRNA) for GSK3β knockdown.
  • Transfected cells with wild-type GSK3β.

Main Results:

  • Tetrandrine induced AKT dephosphorylation and GSK3β activation/nuclear translocation in HT-29 cells.
  • Tetrandrine upregulated p27kip1, leading to cyclin D1 phosphorylation and proteolysis.
  • GSK3β activation by tetrandrine promoted caspase 3 activation and PARP cleavage, key events in apoptosis.
  • Inhibition or knockdown of GSK3β attenuated tetrandrine-induced G1 arrest and apoptosis.
  • Overexpression of GSK3β mimicked tetrandrine's effects, inducing G1 arrest and apoptosis.

Conclusions:

  • Tetrandrine induces G1 cell cycle arrest and apoptosis in human cancer cells via the PI3K/AKT/GSK3β signaling pathway.
  • GSK3β acts as a critical mediator in the anti-cancer effects of tetrandrine.
  • Targeting GSK3β may represent a therapeutic strategy for cancer treatment.

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