Apoptotic effect of eugenol envolves G2/M phase abrogation accompanied by mitochondrial damage and clastogenic effect on cancer cell in vitro

Phytomedicine. 2016 Jun 15;23(7):725-35. doi: 10.1016/j.phymed.2016.03.014. Epub 2016 Apr 16.

Abstract

Background: Eugenol (EUG) is a major phenolic compound present in clove whose anti-cancer properties have been demonstrated previously. These anti-cancer properties may involves the modulation of different mechanisms, including α-estrogen receptor (αER) in luminal breast cancer cells, COX-2 inhibition in melanoma cells or p53 and caspase-3 activation in colon cancer cells.

Hypothesis: EUG promotes a burst in ROS production causing cell-cycle perturbations, mitochondria toxicity and clastogenesis triggering apoptosis in melanoma breast- and cervix-cancer cells in vitro.

Methods: Morphological changes were evaluated through the light- and electronic- microscopy. Cell-cycle, ROS, PCNA and Apoptosis was detected by flow cytometry and clastogenicity was evaluated by Comet-assay.

Results: The results obtained herein pointed out that EUG promotes, increasing ROS production leading to abrogation of G2/M of phase of cell-cycle, and consecutively, clastogenesis in vitro. In addition, EUG induces Proliferation Cell Nuclear Antigen (PCNA) downregulation and decreasing in mitochondria potential (ΔΨm). Of note, a Bax up-regulation was also observed on cells treated with EUG. All of these findings cooperate in order to induce apoptosis in cancer cells.

Conclusion: These promising results presented herein shed new light on the mechanisms of action of EUG suggesting a possible applicability of this phenylpropanoid as adjuvant in anti-cancer therapy.

Keywords: Apoptosis; Cancer; Cell-cycle; Eugenol; Mitochondria potential.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Cell Division / drug effects*
  • Cell Line, Tumor
  • Comet Assay
  • Eugenol / pharmacology*
  • Female
  • G2 Phase / drug effects*
  • Humans
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects*
  • Mutagens / toxicity*
  • Neoplasms / pathology*
  • Proliferating Cell Nuclear Antigen / metabolism
  • Reactive Oxygen Species / metabolism

Substances

  • Antineoplastic Agents, Phytogenic
  • Mutagens
  • Proliferating Cell Nuclear Antigen
  • Reactive Oxygen Species
  • Eugenol