Please use this identifier to cite or link to this item:
https://hdl.handle.net/10316/5799
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. | URI: | https://hdl.handle.net/10316/5799 | DOI: | 10.1016/S0887-2333(01)00019-4 | Rights: | openAccess |
Appears in Collections: | FFUC- Artigos em Revistas Internacionais |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
fileb1575cf798af45bc9b895ab729103cb3.pdf | 137.8 kB | Adobe PDF | View/Open |
SCOPUSTM
Citations
23
checked on Oct 14, 2024
WEB OF SCIENCETM
Citations
22
checked on Jun 2, 2024
Page view(s) 50
556
checked on Oct 15, 2024
Download(s) 50
831
checked on Oct 15, 2024
Google ScholarTM
Check
Altmetric
Altmetric
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.