Olanzapine induced autophagy through suppression of NF-κB activation in human glioma cells

Ying Zhu1, Yi-Fan Zhao1, Rui-Si Liu1

  • 1Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou, China.

Abstract

Insights

Olanzapine inhibits glioma cell growth by activating autophagy through the suppression of NF-κB signaling. This study reveals a novel mechanism for olanzapine

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Biology

Background:

  • Olanzapine previously demonstrated inhibitory effects on glioma cell lines.
  • Autophagy was hypothesized to mediate olanzapine's anti-proliferative effects.
  • Mechanisms of olanzapine-induced autophagy remain unclear.

Purpose of the Study:

  • To elucidate the mechanisms by which olanzapine activates autophagy in glioma cells.
  • To investigate the role of NF-κB signaling in olanzapine-induced autophagy.
  • To evaluate olanzapine as a potential anticancer therapeutic.

Main Methods:

  • Cell viability assays (CCK8, Hoechst 33258, Annexin V-FITC/PI).
  • Western blotting, nuclear separation, and immunofluorescence assays.
  • Investigated NF-κB (p65) and autophagy markers.

Main Results:

  • Olanzapine increased autophagic flux and autophagic vesicles.
  • Autophagy activation correlated with NF-κB inhibition, including p65 nuclear translocation.
  • Olanzapine's autophagy induction was impaired by TNFα cotreatment.
  • Olanzapine inhibited T98 cells expressing MGMT, potentially via NF-κB/MGMT pathway.

Conclusions:

  • Olanzapine induces autophagy by suppressing NF-κB signaling in glioma cells.
  • This pathway provides mechanistic insight into olanzapine's anti-cancer effects.
  • Findings support olanzapine's potential as an anticancer drug.

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