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Ibuprofen-induced Walker 256 tumor cell death: cytochrome c release from functional mitochondria and enhancement by calcineurin inhibition.

Abstract：

:The participation of mitochondria in the mechanism of tumor cell death induced by non-steroid anti-inflammatory drugs is uncertain. Here we show that ibuprofen induces death of Walker 256 tumor cells independently on mitochondrial depolarization as estimated by flow cytometry using DioC(6)(3). Oligomycin increased mitochondrial transmembrane potential in both ibuprofen-treated and non-treated cells, indicating that ATP synthesis was sustained during cell death. Cyclosporin A, but not bongkrekic acid, both mitochondrial permeability transition inhibitors, increased the percentage of cell death in the presence of ibuprofen. FK506, a calcineurin inhibitor like cyclosporin A, also increased ibuprofen-induced cell death. Moreover, we showed that cytochrome c was released during ibuprofen-induced cell death. In conclusion, death of Walker 256 tumor cells induced by ibuprofen does not impair mitochondrial function, involves cytochrome c release and is accompanied by a rescue pathway via calcineurin activation.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

Campos CB,Degasperi GR,Pacífico DS,Alberici LC,Carreira RS,Guimarães F,Castilho RF,Vercesi AE

doi

10.1016/j.bcp.2004.08.006

subject

Has Abstract

pub_date

2004-12-01 00:00:00

pages

2197-206

issue

11

eissn

0006-2952

issn

1873-2968

pii

S0006-2952(04)00583-0

journal_volume

68

pub_type

杂志文章

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