title: 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.
authors.affiliation: Department of Radiation Oncology, Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116027, P.R. China.
authors.forename: Guoquan
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Radiation Oncology, Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116027, P.R. China.
authors.forename: Bingbing
authors.initials: B
authors.lastname: Xie
authors.affiliation: Radiation Oncology Center, People's Liberation Army No. 323 Hospital, Xi'an, Shanxi 710000, P.R. China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Radiation Oncology, Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116027, P.R. China.
authors.forename: Yinghai
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116001, P.R. China.
authors.forename: Yinghui
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Radiation Oncology, Ohio State University, Columbus, OH 43210-1219, USA.
authors.forename: Meng
authors.initials: M
authors.lastname: Xu-Welliver
authors.affiliation: Department of Radiation Oncology, Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116027, P.R. China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Zou
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging*; D000077192:Adenocarcinoma of Lung; D000818:Animals; D045744:Cell Line, Tumor; D030024:Curcuma / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging*; D008516:Medicine, Chinese Traditional; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D054464:Peroxiredoxins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D010936:Plant Extracts / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D011836:Radiation Tolerance / Q000187:drug effects*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D011859:Radiography; D012717:Sesquiterpenes / Q000494:pharmacology*; D053719:Tandem Mass Spectrometry; D014158:Transcription, Genetic / Q000187:drug effects; D014183:Transplantation, Heterologous
chemical_list: D010936:Plant Extracts; D012333:RNA, Messenger; D011838:Radiation-Sensitizing Agents; D012717:Sesquiterpenes; C445979:beta-elemene; C515940:PRDX1 protein, human; D054464:Peroxiredoxins