Please use this identifier to cite or link to this item:
Title: Mitochondrial permeability transition induced by the anticancer drug etoposide
Authors: Custódio, J. B. A. 
Cardoso, C. M. P. 
Madeira, V. M. C. 
Almeida, L. M. 
Keywords: Etoposide; Anticancer; Apoptosis; Liver mitochondria; Mitochondrial permeability transition
Issue Date: 2001
Citation: Toxicology in Vitro. 15:4-5 (2001) 265-270
Abstract: Etoposide (VP-16) is widely used for the treatment of several forms of cancer. The cytotoxicity of VP-16 has been assigned to the induction of apoptotic cell death but the signaling pathway for VP-16-induced apoptosis is essentially unknown. There is some evidence that this process depends on events associated with the loss of mitochondrial membrane potential ([Delta][Psi]) and/or release of apoptogenic factors, putatively as a consequence of mitochondrial permeability transition (MPT) induction. This work evaluates the interference of VP-16 with MPT in vitro, which is characterized by the Ca2+-dependent depolarization of [Delta][Psi], the release of matrix Ca2+ and by extensive swelling of mitochondria. [Delta][Psi] depolarization and Ca2+ release were measured with ion-selective electrodes, and mitochondrial swelling was monitored spectrophotometrically. Incubation of rat liver mitochondria with VP-16 results in a concentration-dependent induction of MPT, evidenced by an increased sensitivity to Ca2+-induced swelling, depolarization of [Delta][Psi], Ca2+ release by mitochondria and stimulation of state 4 oxygen consumption. All of these effects are prevented by preincubating the mitochondria with cyclosporine A, a potent and specific inhibitor of the MPT. Therefore, VP-16 increases the sensitivity of isolated mitochondria to the Ca2+-dependent induction of the MPT. Together, these data provide a possible mechanistic explanation for the previously reported effects of VP-16 on apoptosis induction.
DOI: 10.1016/S0887-2333(01)00019-4
Rights: openAccess
Appears in Collections:FFUC- Artigos em Revistas Internacionais

Files in This Item:
File Description SizeFormat
fileb1575cf798af45bc9b895ab729103cb3.pdf137.8 kBAdobe PDFView/Open
Show full item record


checked on Aug 2, 2022

Page view(s) 50

checked on Aug 17, 2022

Download(s) 50

checked on Aug 17, 2022

Google ScholarTM




Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.