In Silico and In Vitro Evaluation of Cytotoxic Activities of Farnesiferol C and Microlobin on MCF-7, HeLa and KYSE Cell Lines

Drug Res (Stuttg). 2016 Oct;66(10):532-538. doi: 10.1055/s-0042-111200. Epub 2016 Jul 27.

Abstract

Background: Cancer is one of the leading causes of death worldwide. Despite certain advances in cancer therapy, still there is considerable demand for developing efficient therapeutic agents. Nowadays, there is a rising interest in the use of natural-based anti-cancer drugs. In this study, the cytotoxicity of farnesiferol C and microlobin isolated from Ferula szowitsiana was investigated against MCF-7, HeLa and KYSE cancer cell lines. In addition, the mechanism of binding of these compounds to apoptotic proteins (Bax, Bak and Bcl-2) was analyzed by an in silico method. Materials and methods: We used MTT assay in order to assess the cytotoxicity of compounds against cancer cell lines. For in silico study, the AutoDock 4 was adopted. Results and discussion: According to the in vitro findings, in general, farnesiferol C showed significant cytotoxicity at higher concentrations (>50 µM) following 48 and 72 h incubation with the selected cancer cells; however, microlobin exhibited almost no activity at concentrations up to 100 µM. The in silico results revealed that both compounds could bind to Bax more efficiently rather than to Bcl-2 or Bak proteins. Conclusion: The results obtained by our preliminary in vitro and in silico studies suggest that these compounds might induce apoptosis through Bax activation; however further studies, either in vitro or in vivo are needed to clarify these activities.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Coumarins / isolation & purification
  • Coumarins / pharmacology*
  • Dose-Response Relationship, Drug
  • Ferula / chemistry
  • Humans
  • Molecular Docking Simulation*
  • Protein Binding
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Sesquiterpenes / isolation & purification
  • Sesquiterpenes / pharmacology*
  • bcl-2 Homologous Antagonist-Killer Protein / metabolism
  • bcl-2-Associated X Protein / metabolism

Substances

  • Antineoplastic Agents
  • BAK1 protein, human
  • Coumarins
  • Proto-Oncogene Proteins c-bcl-2
  • Sesquiterpenes
  • bcl-2 Homologous Antagonist-Killer Protein
  • bcl-2-Associated X Protein
  • microlobin
  • farnesiferol C