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.

Interplay of DNA methyltransferase 1 and EZH2 through inactivation of Stat3 contributes to β-elemene-inhibited growth of nasopharyngeal carcinoma cells

“…Growing evidence suggests that β-elemene has been shown to be effective against a wide variety of tumors 7–9, 17, 43 . However, there was no published data demonstrating the association and potential of β-elemene in controlling of NPC.…”

“…A large body of evidence demonstrated the significant role of multiple signaling pathways and potential targets (genes or/and proteins) involved in the anti-tumor effects of β-elemene in various cancer types 7, 17, 43, 44 . However, the detailed molecular mechanism underlying this remains largely to be elucidated.…”

Peroxiredoxin 1 – an antioxidant enzyme in cancer

“…As mentioned above, PRDX1 is a potential target for cancer radiotherapy and/or chemotherapy. Several studies have suggested that anticancer molecules/gene reverse radioresistance through targeting PRDX1 on human lung cancer [88][89][90]. Vitamin K3 (vitK3) is a synthetic naphthoquinone exhibiting significant anticancer activity against multiple human cancers both in vitro and in vivo [91][92][93], and its major anticancer mechanism is depended on the generation of ROS [94,95].…”

Chinese Herbal Extractions for Relieving Radiation Induced Lung Injury: A Systematic Review and Meta-Analysis

“…Their extractions tanshinone, LI, and EI relieved RILI in vivo [38] and have antitumor effects against lung cancer [54–56]. EI also enhances the radiosensitivity of lung adenocarcinoma [57]. …”