Withaferin A induces mitochondrial-dependent apoptosis in non-small cell lung cancer cells via generation of reactive oxygen species

J BUON. 2017 Jan-Feb;22(1):244-250.

Abstract

Purpose: Withaferin A (WA) is a bioactive lactone, isolated from natural sources, mainly found in Withania somnifera, and was known to be highly effective against a variety of tumor cells both in vitro and in vivo. Accumulating experimental evidence suggests the involvement of reactive oxygen species (ROS) in WA-mediated cytotoxicity against cancer cells. Hence, the purpose of this study was to investigate the effect of WA in non-small cell lung cancer (NSCLC) cells and also the role of ROC in WA-mediated cytotoxicity.

Methods: In the present study we investigated the cytotoxic potential of WA against NSCLC cell line A549 and also highlighted the mechanism of cytotoxicity of this compound. Non-carcinoma WI-38 and PBMC cell lines were used as controls.

Results: WA treatment resulted in a dose-dependent cytotoxicity in A549 cells, while the non-carcinoma cells WI-38 and PBMC were unaffected. Further experimental approaches revealed that ROS plays a major role in WAinduced apoptosis in NSCLC cells.

Conclusion: WA induces oxidative damage to NSCLC cells with minimum toxicity to normal cells.

MeSH terms

  • Apoptosis / drug effects*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Membrane Potential, Mitochondrial / drug effects
  • Proto-Oncogene Proteins c-bcl-2 / analysis
  • Reactive Oxygen Species / metabolism*
  • Withanolides / pharmacology*
  • bcl-2-Associated X Protein / analysis

Substances

  • BAX protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • Reactive Oxygen Species
  • Withanolides
  • bcl-2-Associated X Protein
  • Caspase 3
  • withaferin A