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Metformin and epothilone A treatment up regulate pro-apoptotic PARP-1, Casp-3 and H2AX genes and decrease of AKT

Aneta Rogalska1, Barbara Bukowska1, Agnieszka Marczak1

  • 1Department of Medical Biophysics, Institute of Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland.

Toxicology in Vitro : an International Journal Published in Association with BIBRA
|November 9, 2017
PubMed

Insights

Combining epothilone A and metformin shows promise for ovarian and liver cancer therapy. This drug combination effectively induces cancer cell death by generating reactive oxygen species (ROS), offering a potential new treatment strategy.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • High mortality in ovarian and liver cancers is often due to chemotherapy resistance.
  • Novel therapeutic strategies are needed to overcome treatment resistance in these cancers.

Purpose of the Study:

  • To investigate the combined genotoxic and pro-oxidant effects of metformin (MET) and epothilone A (A) on cancer cells.
  • To evaluate the potential of this drug combination in inducing apoptosis and overcoming chemoresistance.

Main Methods:

  • HepG2 (liver) and SKOV-3 (ovarian) cancer cells were treated with MET and epothilone A, alone and in combination.
  • Reactive oxygen species (ROS) generation was measured using a fluorescent probe.
  • Apoptosis, cell cycle arrest, and gene expression (caspase-3, PARP-1, H2AX) were analyzed.

Main Results:

  • The combination of epothilone A and MET significantly enhanced apoptosis and induced cell cycle arrest compared to monotherapy.
  • The drug combination increased mRNA levels of key apoptosis markers: caspase-3, poly (ADP-ribose) polymerase-1, and H2AX.
  • Anticancer effects were partially reversed by N-acetylcysteine (NAC), indicating a crucial role for ROS generation.

Conclusions:

  • The combination of epothilone A and metformin demonstrates potent anticancer activity against liver and ovarian cancer cells.
  • ROS generation is a key mechanism underlying the synergistic apoptotic effect of this drug combination.
  • This novel combination therapy holds promise for improving treatment outcomes in ovarian and liver cancer.
Keywords:
ApoptosisCell cycleDNA damageEpothilone AMetformin

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