Chemotherapeutic effect of Zerumbone on melanoma cells through mitochondria-mediated pathways

Clin Exp Dermatol. 2016 Dec;41(8):858-863. doi: 10.1111/ced.12986. Epub 2016 Oct 19.

Abstract

Background: Zerumbone (ZER) is a phytochemical that appears to regulate cell proliferation and apoptosis. It has been reported to have an anti-tumour effect in various malignant cells; however, the effect and the mechanism of ZER on melanoma cells needs to be clarified.

Aim: To explore whether ZER has an effect on human melanoma cells and to identify the mechanisms involved.

Methods: We determined the chemotherapeutic action of ZER on the human malignant melanoma (MM) A375 cell line by CCK-8 immunohistochemistry, Hoechst 33342 staining and flow cytometry analysis. We also investigated the signalling pathways by which ZER induces apoptosis in A375 cells, using western blotting, reverse transcription PCR and caspase-3 activity analysis.

Results: ZER induced significant cytotoxic action in A375 cells. Hoechst 33342 staining and flow cytometry apoptosis analysis further demonstrated that ZER induced apoptosis in A375 cells. Treatment with ZER downregulated Bcl-2 gene and protein levels, upregulated Bax and Cytochrome c gene and protein levels, and activated Caspase-3.

Conclusions: ZER might have a chemotherapeutic effect on human melanoma cells through mitochondria-mediated pathways.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Blotting, Western
  • Caspase 3 / metabolism
  • Cell Line, Tumor / drug effects
  • Flow Cytometry
  • Humans
  • Immunohistochemistry
  • Melanoma / drug therapy*
  • Melanoma / pathology
  • Mitochondria / drug effects*
  • Phytochemicals / pharmacology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sesquiterpenes / pharmacology*
  • Signal Transduction / drug effects

Substances

  • Antineoplastic Agents
  • Phytochemicals
  • Sesquiterpenes
  • zerumbone
  • Caspase 3