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  • Title: Nuclear factor-kappaB inhibition by parthenolide potentiates the efficacy of Taxol in non-small cell lung cancer in vitro and in vivo.
    Author: Zhang D, Qiu L, Jin X, Guo Z, Guo C.
    Journal: Mol Cancer Res; 2009 Jul; 7(7):1139-49. PubMed ID: 19584264.
    Abstract:
    In this study, we have examined the molecular events induced by parthenolide, a sesquiterpene lactone, and explored possible mechanisms of resistance and sensitization of tumor cells to Taxol. We showed that parthenolide could antagonize Taxol-mediated nuclear factor-kappaB (NF-kappaB) nuclear translocation and activation and Bcl-xl up-regulation by selectively targeting I-kappaB kinase activity. In A549 cells, inhibition of nuclear factor-kappaB by parthenolide resulted in activation of the mitochondrial death pathway to promote cytochrome c release and caspase 3 and 9 activation. In contrast, Taxol alone induced apoptosis via a pathway independent of mitochondria cytochrome c cascade. In addition, depletion of Bcl-xl rescued the apoptotic response to Taxol. Moreover, treatment with parthenolide increased the efficacy of the Taxol-induced inhibition of A549 tumor xenografts in mice. This study elucidated the cellular responses induced by parthenolide that decrease the threshold of mitochondria-dependent apoptosis in the treatment of non-small cell lung cancer cells.
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