Cbl-regulated Akt and ERK signals are involved in β-elemene-induced cell apoptosis in lung cancer cells

Mol Med Rep. 2011 Nov-Dec;4(6):1243-6. doi: 10.3892/mmr.2011.548. Epub 2011 Aug 11.

Abstract

β-elemene is an active component of a natural plant-derived antineoplastic agent. Although the anticancer activity of β-elemene has been reported, its antitumor mechanism has not been elucidated. The aim of the present study was to investigate how Cbl-regulated Akt and ERK affect β-elemene-induced cell apoptosis in lung cancer cells. In the present study, β-elemene induced cell apoptosis in a dose-dependent manner in A549 cells. Moreover, β-elemene decreased bcl-2 expression, increased bax expression and caused the cleavage of PARP. However, β-elemene also induced the phosphorylation of Akt and ERK in a short period of time. The inhibition of Akt and ERK activation rapidly enhanced β-elemene-induced apoptosis, and the up-regulation of c-Cbl and Cbl-b expression was also detected. These results suggest that Cbl-regulated Akt and ERK signals are involved in β-elemene-induced cell apoptosis in lung cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Chromones / pharmacology
  • Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Flavonoids / pharmacology
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / metabolism*
  • Morpholines / pharmacology
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / metabolism
  • Proto-Oncogene Proteins c-cbl / metabolism*
  • Sesquiterpenes / pharmacology*
  • Sesquiterpenes / therapeutic use
  • Signal Transduction / drug effects*

Substances

  • Antineoplastic Agents
  • Chromones
  • Flavonoids
  • Morpholines
  • Sesquiterpenes
  • beta-elemene
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Proto-Oncogene Proteins c-cbl
  • Proto-Oncogene Proteins c-akt
  • Extracellular Signal-Regulated MAP Kinases
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one