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Alantolactone triggers oxeiptosis in human ovarian cancer cells via Nrf2 signaling pathway

Mahdieh Nasirzadeh1, Somayeh Atari Hajipirloo1, Shiva Gholizadeh-Ghaleh Aziz2,1,3,4

  • 1Department of Clinical Biochemistry, Faculty of Medicine, Urmia University Medical Sciences (UMSU), Urmia, Iran.

Biochemistry and Biophysics Reports
|September 15, 2023
PubMed
Abstract

Insights

Alantolactone (ALT) shows potential in treating ovarian cancer by inducing cell death through increased reactive oxygen species (ROS). This study investigated ALT

Area of Science:

  • Oncology
  • Cell Biology
  • Biochemistry

Background:

  • Reactive Oxygen Species (ROS) are implicated in cancer cell proliferation.
  • Alantolactone (ALT) selectively promotes ROS generation in cancer cells.
  • Oxeiptosis is a novel cell death pathway triggered by high intracellular ROS levels.

Purpose of the Study:

  • To investigate the effect of Alantolactone (ALT) on the molecular mechanisms of oxeiptosis in ovarian cancer.
  • To explore ALT's potential as a novel therapeutic agent for ovarian cancer.

Main Methods:

  • MTT assay was used to assess SKOV3 cell viability.
  • Real-time PCR and Western blotting were employed to analyze gene and protein expression levels of key molecules involved in ROS and cell death pathways (Nrf2, KEAP1, PGAM5, AIFM1, GSS, GPX).

Main Results:

  • Alantolactone (ALT) inhibited SKOV3 cell proliferation in a time- and dose-dependent manner (IC50 = 32 μM at 24h).
  • ALT significantly downregulated mRNA and protein levels of Nrf2, GSH, and GPX, while upregulating PGAM5 and KEAP1.
  • ALT treatment led to dephosphorylation of PS116-AIFM1 and an elevation in total AIFM1 protein levels.

Conclusions:

  • Alantolactone (ALT) induces ovarian cancer cell death via ROS-mediated oxeiptosis.
  • ALT demonstrates potential as a therapeutic option for ovarian cancer treatment.
Keywords:
AlantolactoneNrf2 signaling pathwayOvarian cancerOxeiptosis

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