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Ursolic acid promotes cancer cell death by inducing Atg5-dependent autophagy

Shuilong Leng1, Yanli Hao, Daobing Du

  • 1Department of Human Anatomy, Guangzhou Medical University, Guangzhou, Guangdong, People's Republic of China.

International Journal of Cancer
|June 6, 2013
PubMed

Insights

Ursolic acid (UA) triggers autophagy, a cell-death process, in cervical cancer cells, reducing tumor growth. This autophagy, mediated by Atg5, offers a new therapeutic strategy for cancer treatment.

Area of Science:

  • Oncology
  • Cell Biology
  • Biochemistry

Background:

  • Ursolic acid (UA) exhibits anticancer properties, but its mechanisms remain unclear.
  • While some UA anticancer effects are linked to apoptosis, this study explores alternative pathways.
  • Cervical cancer remains a significant health concern, necessitating novel therapeutic approaches.

Purpose of the Study:

  • To investigate the role of autophagy in the anticancer effects of ursolic acid (UA) on TC-1 cervical cancer cells.
  • To determine whether UA-induced cell death occurs via apoptosis or autophagy.
  • To identify key autophagy-related genes involved in UA's mechanism of action.

Main Methods:

  • TC-1 cells and mouse embryonic fibroblast (MEF) cells (Atg5+/+ and Atg5-/-) were treated with UA.
  • Apoptosis was assessed using Annexin V/propidium iodide staining, DNA fragmentation, and Western blotting.
  • Autophagy was evaluated by monitoring LC3 (microtubule-associated protein 1A/1B-light chain 3) puncta, LC3II levels, and transmission electron microscopy.
  • Inhibitors like wortmannin and gene silencing (siRNA for Atg5 and BECN1) were employed to modulate autophagy pathways.

Main Results:

  • UA treatment induced autophagy, evidenced by increased LC3 puncta and LC3II levels in TC-1 cells, without inducing apoptosis.
  • Autophagy inhibition (wortmannin or Atg5 siRNA) reduced UA-induced cytotoxicity and LC3II expression.
  • MEF cells lacking Atg5 (Atg5-/-) showed significantly reduced LC3II and increased survival upon UA treatment compared to wild-type MEF cells.
  • Silencing BECN1 did not affect UA-induced autophagy or cell survival.

Conclusions:

  • Autophagy, specifically dependent on Atg5, is a primary mechanism for UA-induced cell death in TC-1 cervical cancer cells.
  • UA-induced autophagic cell death presents a potential therapeutic strategy, distinct from apoptosis-based treatments.
  • Targeting Atg5 may enhance the efficacy of ursolic acid in cancer therapy.
Keywords:
Atg5TC-1apoptosisautophagyursolic acid

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