Brevifoliol ester induces apoptosis in prostate cancer cells by activation of caspase pathway

Chem Biol Drug Des. 2020 Jan;95(1):150-161. doi: 10.1111/cbdd.13631. Epub 2019 Oct 20.

Abstract

Prostate cancer is fourth most abundant cancer type around the globe. Brevifoliol, a rearranged taxoid from Taxus walllichiana needles has been derivatized as C5 esters using Steglich esterification reaction. Seventeen diverse analogues were evaluated against a panel of human cancer cell lines by MTT assay. Among these, two of the semi-synthetic analogues, that is, 13 and 16 exhibited potent cytotoxicity, selectively against PC-3, prostate cancer cell lines. In cell cycle analysis, analogue 13 induced S and G2/M phase arrest and induced apoptosis by activating caspase-3. Compound 13 showed moderate efficacy in in-vivo Ehrlich ascites carcinoma in Swiss albino mice. Further, compound 13 was found to be safe in Swiss albino mice up to 1,000 mg/kg dose in acute oral toxicity. Brevifoliol ester 13 may further be optimized for better efficacy.

Keywords: Ehrlich ascites carcinoma; acute oral toxicity; anticancer; apoptosis; brevifoliol analogues.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetic Acid / chemistry
  • Animals
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Benzoic Acid / chemistry
  • Drug Screening Assays, Antitumor
  • Esterification
  • Esters / chemistry*
  • Humans
  • Male
  • Mice
  • Molecular Docking Simulation
  • Neoplasms, Experimental / drug therapy
  • PC-3 Cells
  • Plant Extracts / chemistry*
  • Plant Extracts / pharmacology
  • Prostatic Neoplasms / drug therapy*
  • Taxoids / chemistry*
  • Taxoids / pharmacology
  • Taxus / chemistry

Substances

  • Antineoplastic Agents
  • Esters
  • Plant Extracts
  • Taxoids
  • brevifoliol
  • Benzoic Acid
  • Acetic Acid