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Shikonin kills glioma cells through necroptosis mediated by RIP-1

Chuanjiang Huang1, Yinan Luo, Jingwei Zhao

  • 1Department of Neurosurgery, First Bethune hospital of Jilin University, Changchun, China.

Plos One
|July 11, 2013
PubMed
Abstract

Insights

Shikonin induces necroptosis, a programmed cell death, in glioma cells. This process involves the RIP-1 pathway and oxidative stress, offering potential therapeutic insights.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • Shikonin exhibits differential effects on cell death, inducing necroptosis in leukemia but apoptosis in glioma cells.
  • Clarifying shikonin's impact on glioma cell death mechanisms is crucial.

Purpose of the Study:

  • To determine if shikonin induces necroptosis in glioma cells.
  • To investigate the underlying molecular mechanisms of shikonin-induced cell death in glioma.

Main Methods:

  • Utilized C6 and U87 glioma cell lines.
  • Assessed cell viability (MTT), cell death modes (flow cytometry), morphology (microscopy), reactive oxygen species (ROS) levels, and RIP-1 protein expression (western blotting).
  • Employed necroptosis inhibitor necrostatin-1 and pan-caspase inhibitor z-VAD-fmk.

Main Results:

  • Shikonin induced dose- and time-dependent cell death in both cell lines.
  • Cell death was inhibited by necrostatin-1 but not z-VAD-fmk, indicating necroptosis.
  • Shikonin increased ROS levels and RIP-1 expression, both of which were attenuated by necrostatin-1 and N-acetylcysteine (NAC).
  • Blocking ROS with NAC rescued shikonin-induced cell death.

Conclusions:

  • Shikonin primarily induces necroptosis in C6 and U87 glioma cells.
  • Both the RIP-1 pathway and oxidative stress are key players in shikonin-induced necroptosis.

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