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Pristimerin triggers AIF-dependent programmed necrosis in glioma cells via activation of JNK

Hongwei Zhao1, Chen Wang1, Bin Lu1

  • 1Department of Neurosurgery, First Hospital of Jilin University, Changchun 130021, China.

Cancer Letters
|February 9, 2016
PubMed

Insights

Pristimerin induces programmed necrosis (necroptosis) in glioma cells by activating JNK, leading to mitochondrial dysfunction and AIF nuclear translocation. This natural compound shows potential for glioma cancer treatment.

Area of Science:

  • Oncology
  • Cell Biology
  • Biochemistry

Background:

  • Programmed necrosis is a novel cell death pathway with therapeutic potential for cancer.
  • Pristimerin exhibits anti-tumor properties, but its precise mechanism of action is not fully understood.

Purpose of the Study:

  • To investigate the anti-glioma effects of pristimerin and elucidate its underlying molecular mechanisms.
  • To determine if pristimerin induces programmed necrosis in glioma cells.

Main Methods:

  • Glioma cell lines and a xenograft mouse model were used to assess pristimerin's efficacy.
  • Key molecular markers including JNK, AIF, Bax/Bcl-2 ratio, mitochondrial membrane potential, ROS, and GSH were analyzed.
  • RNA interference (siRNA) and pharmacological inhibitors were employed to dissect the signaling pathways involved.

Main Results:

  • Pristimerin inhibited glioma cell viability and xenograft tumor growth.
  • Pristimerin induced glioma cell necrosis, characterized by mitochondrial depolarization, ROS overproduction, and reduced GSH.
  • The mechanism involves JNK activation, ROS overproduction, mitochondrial dysfunction, and subsequent AIF nuclear translocation, leading to AIF-dependent necroptosis.

Conclusions:

  • Pristimerin triggers AIF-dependent necroptosis in glioma cells through JNK-mediated mitochondrial dysfunction and ROS generation.
  • These findings highlight pristimerin as a promising therapeutic agent for glioma treatment.
Keywords:
Apoptosis inducing factor (AIF)GliomaPristimerinProgrammed necrosisROSc-Jun terminal kinase (JNK)

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