Synergistic inhibition of mesothelioma cell growth by the combination of clofarabine and resveratrol involves Nrf2 downregulation
자연과학 > 화학
( Yoon Jin Lee ) , ( Jae Hyuk Im ) , ( David M Lee ) , ( Ji Sung Park ) , ( Seong Youn Won ) , ( Moon Kyun Cho ) , ( Hae Seon Nam ) , ( Yong Jin Lee ) , ( Sang Han Lee )
생화학분자생물학회(구 한국생화학분자생물학회)
BMB Reports 2012년, 제45권 제11호, 647~652쪽(총6쪽)
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    We previously reported that MSTO-211H cells have a higher capacity to regulate Nrf2 activation in response to changes in the cellular redox environment. To further characterize its biological significance, the response of Nrf2, a transcription factor that regulates ARE-containing genes, on the synergistic cytotoxic effect of clofarabine and resveratrol was investigated in mesothelioma cells. The combination treatment showed a marked growth-inhibitory effect, which was accompanied by suppression of Nrf2 activation and decreased expression of heme oxygenase-1 (HO-1). While transient overexpression of Nrf2 conferred protection against the cytotoxicity caused by their combination, knockdown of Nrf2 expression using siRNA enhanced their cytotoxic effect. Pretreatment with Ly294002, a PI3K inhibitor, augmented the decrease in HO-1 level by their combination, whereas no obvious changes were observed in Nrf2 levels. Altogether, these results suggest that the synergistic cytotoxic effect of clofarabine and resveratrol was mediated, at least in part, through suppression of Nrf2 signaling.
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