Colocalization of BAX with BID and VDAC-1 in nimesulide-induced apoptosis of human colon adenocarcinoma COLO 205 cells
作者:
Michat Godlewski,
Barbara Gajkowska,
Monika Lamparska-Przybysz,
Tomasz Motyl,
期刊:
Anti-Cancer Drugs
(OVID Available online 2002)
卷期:
Volume 13,
issue 10
页码: 1017-1029
ISSN:0959-4973
年代: 2002
出版商: OVID
关键词: Apoptosis;BAX;BID;COLO 205;nimesulide;prostaglandin E2;VDAC-1
数据来源: OVID
摘要:
Cyclooxygenase (COX)-2 inhibitors that belong to non-steroid anti-inflammatory drug family have been shown to have an apoptosis-inducing effect on neoplastic cells. In the present study the effect of nimesulide (NIM), a specific COX-2 inhibitor, on apoptosis and interactions between BCL-2 family death promoters BAX and BID and BAX and VDAC-1 were examined in human colon adenocarcinoma COLO 205 cells. Laser scanning cytometry was applied for the measurement of expression and aggregation of apoptosis-related proteins and quantitative analysis of NIM-induced apoptosis. Double-staining immunoconfocal and immunoelectron microscopy were used for subcellular colocalization of examined proteins. NIM induced apoptosis of COLO 205 cells in a dose-dependent manner. This was accompanied by: (1) a decrease in intracellular prostaglandin (PG) E2content; (2) subcellular redistribution and aggregation of BAX and BID on organellar membranes and within the nucleus; (3) colocalization of BAX with BID and BAX with VDAC-1 on organelles; and (4) survival of cells with the highest BCL-2 aggregation. A similar pattern of subcellular redistribution and colocalization of BAX with BID and BAX with VDAC-1 suggests that BAX (in association with BID) controls the function of VDAC-1 and its permeability for apoptogenic factors released from mitochondria of COLO 205 cells stimulated to apoptosis with NIM.
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