alpha-Bisabolol induces dose- and time-dependent apoptosis in HepG2 cells via a Fas- and mitochondrial-related pathway, involves p53 and NFkappaB

Biochem Pharmacol. 2010 Jul 15;80(2):247-54. doi: 10.1016/j.bcp.2010.03.021. Epub 2010 Mar 25.

Abstract

In this study, the apoptotic effect of alpha-bisabolol, a sesquiterpene, against human liver carcinoma cell line HepG2 was investigated. MTT assay showed alpha-bisabolol could effectively induce cytotoxicity in several human cancer cell lines (PC-3, Hela, ECA-109 and HepG2). The results of nuclei morphology examination, DNA fragmentation detection, flow cytometry analysis and cleavage of poly(ADP-ribose) polymerase and caspases indicated alpha-bisabolol might induce dose- and time-dependent apoptosis in HepG2 cells. Western blot data also showed a cascade activation of caspases-8,-9,-3 and promoted expression of Fas, implying caspase-8 might function as an upstream regulator, and the Fas-related pathway might be involved in this process. Preparation of mitochondrial/cytosol fraction followed with immunoblot analysis showed the release of chromosome c from mitochondria, down-regulated expression of Bcl-2 and translocation of Bax, Bak and Bid, suggesting the mitochondrial-related pathway might be involved in alpha-bisabolol-induced apoptosis either. Detection of accumulation of nuclear wild-type p53 and up-regulated expression of NFkappaB indicated these two key regulator with transcriptional decision-making function in various signaling pathways might also play a role in alpha-bisabolol-induced apoptosis in HepG2 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Cell Cycle / drug effects
  • Cell Cycle / physiology
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Female
  • Formazans / metabolism
  • Hep G2 Cells / metabolism
  • Hep G2 Cells / pathology*
  • Humans
  • Male
  • Mitochondria, Liver / metabolism*
  • Monocyclic Sesquiterpenes
  • NF-kappa B / metabolism*
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases / drug effects
  • Poly(ADP-ribose) Polymerases / metabolism
  • Sesquiterpenes / pharmacology*
  • Tetrazolium Salts / metabolism
  • Time Factors
  • Tumor Suppressor Protein p53 / metabolism*
  • fas Receptor / metabolism*

Substances

  • Antineoplastic Agents
  • FAS protein, human
  • Formazans
  • Monocyclic Sesquiterpenes
  • NF-kappa B
  • Sesquiterpenes
  • Tetrazolium Salts
  • Tumor Suppressor Protein p53
  • fas Receptor
  • MTT formazan
  • bisabolol
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases