Down-regulation of survivin and hypoxia-inducible factor-1 α by β-elemene enhances the radiosensitivity of lung adenocarcinoma xenograft

Cancer Biother Radiopharm. 2012 Feb;27(1):56-64. doi: 10.1089/cbr.2011.1003. Epub 2012 Jan 16.

Abstract

Elemene (1-methyl-1-vinyl-2,4-diisopropenyl-cyclohexane) is a naturally occurring compound that can be isolated from the traditional Chinese medicinal herb Curcuma wenyujin. β-elemene, its active component, has recently been demonstrated to enhance the radiosensitivity of human cancer cell lines in vitro and of one animal tumor in vivo. The underlying mechanism, however, is still unclear. In this study, we demonstrated for the first time that β-elemene significantly improves the radiosensitivity of A549 lung adenocarcinoma xenograft in vivo as measured by tumor regrowth delay experiments. Our results showed that β-elemene, at 45 mg/kg, significantly inhibited radiation-induced expression of survivin and hypoxia-inducible factor (HIF)-1 α proteins. Because HIF-1 α is known to regulate survivin transcription and acts as upstream regulator of survivin, it is possible that β-elemene regulates the transcription of survivin through HIF-1 α. Our study suggests that β-elemene is a promising drug to enhance tumor radioresponse, and survivin and HIF-1 α are novel targets of β-elemene.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / radiotherapy*
  • Adenocarcinoma of Lung
  • Animals
  • Cell Line, Tumor
  • Combined Modality Therapy
  • Down-Regulation / drug effects
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Immunohistochemistry
  • Inhibitor of Apoptosis Proteins / genetics
  • Inhibitor of Apoptosis Proteins / metabolism*
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / radiotherapy*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Radiation-Sensitizing Agents / pharmacology*
  • Sesquiterpenes / pharmacology*
  • Survivin
  • Xenograft Model Antitumor Assays

Substances

  • BIRC5 protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Inhibitor of Apoptosis Proteins
  • Radiation-Sensitizing Agents
  • Sesquiterpenes
  • Survivin
  • beta-elemene