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Apoptosis induced in HepG2 cells by the synthetic cannabinoid WIN: involvement of the transcription factor PPARgamma

Michela Giuliano1, Ornella Pellerito, Patrizia Portanova

  • 1Dipartimento di Scienze Biochimiche, Università di Palermo, Via del Vespro 129, 90127 Palermo, Italy.

Biochimie
|December 9, 2008
PubMed

Insights

Cannabinoids like WIN 55,212-2 induce apoptosis in liver cancer cells by activating specific pathways. This research suggests a potential therapeutic role for cannabinoids in treating hepatic cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Cannabinoids are known to inhibit tumor cell growth and induce apoptosis.
  • Understanding the specific mechanisms and pathways involved is crucial for therapeutic development.

Purpose of the Study:

  • To investigate the effects of WIN 55,212-2, a cannabinoid receptor agonist, on hepatoma HepG2 cells.
  • To elucidate the signal transduction pathway mediating WIN 55,212-2-induced apoptosis.

Main Methods:

  • Treatment of HepG2 cells with WIN 55,212-2.
  • Analysis of apoptosis-related gene and protein expression (Bax, Bcl-X(S), t-Bid, survivin, Bcl-2).
  • Assessment of JNK/p38 MAPK pathway activation, mitochondrial membrane potential, and PPARgamma levels.
  • Use of PPARgamma antagonists (GW9662, T0070907) to evaluate pathway involvement.

Main Results:

  • WIN 55,212-2 induced apoptosis in HepG2 cells, altering expression of pro-apoptotic and anti-apoptotic factors.
  • Apoptosis was linked to JNK/p38 MAPK activation and mitochondrial depolarization.
  • WIN 55,212-2 increased PPARgamma levels in a dose- and time-dependent manner.
  • PPARgamma antagonists significantly inhibited WIN 55,212-2's effects on cell viability and key signaling molecules.

Conclusions:

  • WIN 55,212-2 triggers apoptosis in hepatoma cells through the activation of the JNK/p38 MAPK pathway.
  • PPARgamma plays a critical role in mediating WIN 55,212-2-induced apoptosis in HepG2 cells.
  • These findings suggest a potential therapeutic application of WIN 55,212-2 in hepatic cancer treatment.

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