Cryptotanshinone induces melanoma cancer cells apoptosis via ROS-mitochondrial apoptotic pathway and impairs cell migration and invasion

Biomed Pharmacother. 2016 Aug:82:319-26. doi: 10.1016/j.biopha.2016.05.015. Epub 2016 May 24.

Abstract

Melanoma is the most serious type of skin cancer because it is highly frequency of drug resistance and can spread earlier and more quickly than other skin cancers. The objective of this research was to investigate the anticancer effects of cryptotanshinone on human melanoma cells in vitro, and explored its mechanisms of action. Our results have shown that cryptotanshinone could inhibit cell proliferation in human melanoma cell lines A2058, A375, and A875 in a dose- and time-dependent manner. In addition, flow cytometry assay showed that cryptotanshinone inhibited the proliferation of human melanoma cell line A375 by blocking cell cycle progression in G2/M phase and inducing apoptosis in a concentration-dependent manner. Moreover, western blot analysis indicated that the occurrence of its apoptosis was associated with upregulation of cleaved caspases-3 and pro-apoptotic protein Bax while downregulation of anti-apoptotic protein Bcl-2. Meanwhile, cryptotanshinone could decrease the levels of reactive oxygen species (ROS). Furthermore, cryptotanshinone also blocked A375 cell migration and invasion in vitro which was associated with the downregulation with MMP-9. Taken together, these results suggested that cryptotanshinone might be a potential drug in human melanoma treatment by inhibiting proliferation, inducing apoptosis via ROS-mitochondrial apoptotic pathway and blocking cell migration and invasion.

Keywords: Apoptosis; Cell cycle; Cryptotanshinone; Melanoma; Migration and invasion.

MeSH terms

  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects
  • Cell Shape / drug effects
  • Cell Survival / drug effects
  • G2 Phase Cell Cycle Checkpoints / drug effects
  • Humans
  • Melanoma / metabolism*
  • Melanoma / pathology*
  • Mitochondria / drug effects
  • Mitochondria / metabolism*
  • Neoplasm Invasiveness
  • Phenanthrenes / chemistry
  • Phenanthrenes / pharmacology*
  • Reactive Oxygen Species / metabolism*
  • Signal Transduction / drug effects
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology
  • Tumor Stem Cell Assay

Substances

  • Phenanthrenes
  • Reactive Oxygen Species
  • cryptotanshinone