Evaluation of cytotoxic and apoptotic effects of individual and mixed 7-ketophytosterol oxides on human intestinal carcinoma cells

J Agric Food Chem. 2015 Jan 28;63(3):1035-41. doi: 10.1021/jf505079v. Epub 2015 Jan 13.

Abstract

Phytosterol oxidation products (POPs) are constituents of the human diet. Definitive information on the toxic or biological effects of POPs is limited and in some cases contradictory. This study evaluates the cytotoxicity of four individual 7-ketophytosterol oxides, including 7-ketositosterol (7K-SI), 7-ketocampesterol (7K-CA), 7-ketobrassicasterol (7K-BR), 7-ketostigmasterol (7K-ST), and a mixture of 7-ketophytosterols (7K-MIX) toward a human intestinal carcinoma (HIC) cell line. Results showed that all tested compounds reduced cell proliferation in a dose-dependent manner; especially 7K-SI and 7K-CA exhibited higher activities. Both compounds increased early apoptotic cells and caused cell cycle arrest in the G1 phase with cell accumulation in the S phase. No evidence of cell death was observed induced by 7K-ST and 7K-MIX. Furthermore, 7K-SI, 7K-CA, and 7K-BR induced apoptosis by enhancing caspase-3 activity and the modulatory effects of Bcl-2, while 7K-ST and 7K-MIX did not involve caspase-3 activation and Bcl-2 down-regulation.

Keywords: 7-ketophytosterol oxides; HIC cells; apoptosis; cell cycle; cytotoxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Caspase 3 / metabolism
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • G1 Phase / drug effects
  • Humans
  • Intestinal Neoplasms / chemistry
  • Intestinal Neoplasms / pathology*
  • Proto-Oncogene Proteins c-bcl-2 / analysis
  • S Phase / drug effects
  • Sitosterols / pharmacology*

Substances

  • 7-ketositosterol
  • Antineoplastic Agents
  • Proto-Oncogene Proteins c-bcl-2
  • Sitosterols
  • Caspase 3