Dysfunctional Apoptosome Activation in Ovarian Cancer: Implications for Chemoresistance

摘要: Alterations in the regulation of apoptosis may contribute to pathogenesis cancer and resistance tumor cells chemotherapy. In mammalian cells, nonreceptor-mediated occurs predominantly via assembly a cytochrome c-dependent apoptosome complex containing caspase-9 apoptotic protease-activating factor-1 (Apaf-1). We show here that cytosolic extracts from human ovarian carcinoma cell lines primary samples are deficient their ability activate procaspase-9 presence c dATP when compared with control extracts. SKOV3, line diminished activity, was significantly more resistant chemotherapy-induced than functional Apaf-1 activity. This dysfunctional activity not explained by reduced expression levels or Apaf-1. Moreover, known inhibitors apoptosome, including heat shock protein 70, 90, X-linked inhibitor apoptosis, did correlate apoptosome. an retains form oligomer; however, there is amount The reduction SKOV3 associated caspase-3 Dysfunctional activation both chemoresistance.