A novel copper(I) complex induces ER-stress-mediated apoptosis and sensitizes B-acute lymphoblastic leukemia cells to chemotherapeutic agents
作者： Roberta Bortolozzi , Giampietro Viola , Elena Porcù , Francesca Consolaro , Cristina Marzano
关键词: Unfolded protein response 、 Biology 、 Cycloheximide 、 Apoptosis 、 Cell 、 Proteasome 、 Cancer cell 、 Programmed cell death 、 Cell culture 、 Molecular biology
摘要: A phosphine copper(I) complex [Cu(thp)4][PF6] (CP) was recently identified as an efficient in vitro antitumor agent. In this study, we evaluated the antiproliferative activity of CP leukemia cell lines finding a significant efficacy, especially against SEM and RS4;11 cells. Immunoblot analysis showed activation caspase-12 caspase-9 two effector caspase-3 -7, suggesting that death occurred caspase-dependent manner. Interestingly did not observe mitochondrial involvement process death. Measures on semipurified proteasome from extracts demonstrated chymotrypsin-, trypsin- caspase-like decreased presence CP. Moreover, found accumulation ubiquitinated proteins remarkable increase ER stress markers: GRP78, CHOP, spliced form XBP1. Accordingly, protein synthesis inhibitor cycloheximide significantly protected cancer cells CP-induced death, machinery involved. well agreement with results obtained stabilized lines, induced ER-stress apoptosis also primary B-acute lymphoblastic patients. Importantly, combination some chemotherapeutic drugs displayed good synergy strongly affected survival both
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