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Role of oxidative stress, endoplasmic reticulum stress and ERK activation in triptolide-induced apoptosis

Bee-Jen Tan1, Gigi N C Chiu

  • 1Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore 117543, Republic of Singapore.

International Journal of Oncology
|March 8, 2013
PubMed

Insights

Triptolide activates the ERK pathway, a key signaling cascade, leading to breast cancer cell death. This study reveals triptolide

Area of Science:

  • Pharmacology
  • Molecular Biology
  • Cancer Research

Background:

  • Triptolide, isolated from Tripterygium wilfordii, exhibits potent anticancer activity.
  • It targets multiple molecular pathways, including mitogen-activated protein kinases.
  • The ERK pathway's role in cell proliferation and death is complex and not fully understood in relation to triptolide.

Purpose of the Study:

  • To investigate the effect of triptolide on ERK signaling in breast cancer cells.
  • To elucidate the role of ERK activation in triptolide-induced apoptosis.
  • To identify upstream signaling events triggering ERK activation by triptolide.

Main Methods:

  • Treatment of MDA-MB-231 breast cancer cells with triptolide.
  • Analysis of ERK pathway activation (phosphorylation) and downstream targets.
  • Investigation of reactive oxygen species (ROS) generation and endoplasmic reticulum (ER) stress.
  • Use of MEK inhibitor U0126 to probe signaling pathways.

Main Results:

  • Triptolide induced dose- and time-dependent ERK activation in breast cancer cells.
  • ERK activation was essential for triptolide-mediated caspase-dependent apoptosis.
  • Triptolide modulated Bax expression but not Bcl-xL.
  • Upstream signals involved ROS generation and ER stress via the PERK‑eIF2α pathway.

Conclusions:

  • Triptolide activates the ERK pathway, contributing to apoptosis in breast cancer cells.
  • ERK activation is a critical mediator of triptolide's cytotoxic effects.
  • ROS generation and ER stress are upstream events in triptolide-induced ERK activation.

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