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Downregulation of peroxiredoxin-1 by β-elemene enhances the radiosensitivity of lung adenocarcinoma xenografts.

Abstract
β-elemene, the active component of elemene (1-methyl-1-vinyl-2,4-diisopropenyl-cyclohexane), is a naturally occurring compound isolated from the traditional Chinese medicinal herb Curcuma wenyujin. Studies have confirmed that β-elemene enhances the radiosensitivity of lung cancer cell lines such as A549, by multiple pathways; however, their underlying mechanisms and pathways are yet to be elucidated. In the present study, two-dimensional differential in-gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry were used to profile the different proteins in A549 cell xenograft models of both treatment groups. The protein/mRNA expression was assessed by reverse transcription-polymerase chain reaction and western blotting techniques in tumor samples from all treatment groups. As a critical player in redox regulation of cancer cells, inhibition of peroxiredoxin-1 (Prx-1) may be an effective option for enhancing the tumor response to radiation. We further verified Prx-1 expression at the transcription and translation levels. β-elemene at a dose of 45 mg/kg had little effect on the Prx-1 protein expression, which was correlated with a moderate antitumor effect. However, a 45 mg/kg dose of β-elemene significantly inhibited the Prx-1 mRNA expression, thereby suggesting a possible influence on the transcriptional process, and radiation significantly increased the Prx-1 mRNA/protein expression compared to the control group (p<0.01). Notably, Prx-1 mRNA/protein expression was significantly lower in the β-elemene/radiation co-treatment group compared to the baseline levels in the control group (p<0.01). These results suggest that radiation-induced Prx-1 expression is directly or indirectly suppressed by β-elemene, thus suggesting a new pathway by which to reverse radioresistance.
AuthorsGuoquan Li, Bingbing Xie, Xiaolong Li, Yinghai Chen, Yinghui Xu, Meng Xu-Welliver, Lijuan Zou
JournalOncology reports (Oncol Rep) Vol. 33 Issue 3 Pg. 1427-33 (Mar 2015) ISSN: 1791-2431 [Electronic] Greece
PMID25607351 (Publication Type: Journal Article)
Chemical References
  • Plant Extracts
  • RNA, Messenger
  • Radiation-Sensitizing Agents
  • Sesquiterpenes
  • beta-elemene
  • PRDX1 protein, human
  • Peroxiredoxins
Topics
  • Adenocarcinoma (diagnostic imaging)
  • Adenocarcinoma of Lung
  • Animals
  • Cell Line, Tumor
  • Curcuma (metabolism)
  • Down-Regulation
  • Female
  • Humans
  • Lung Neoplasms (diagnostic imaging)
  • Medicine, Chinese Traditional
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Transplantation
  • Peroxiredoxins (antagonists & inhibitors, biosynthesis, genetics)
  • Plant Extracts (pharmacology)
  • RNA, Messenger (biosynthesis)
  • Radiation Tolerance (drug effects)
  • Radiation-Sensitizing Agents (pharmacology)
  • Radiography
  • Sesquiterpenes (pharmacology)
  • Tandem Mass Spectrometry
  • Transcription, Genetic (drug effects)
  • Transplantation, Heterologous

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