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Induction of apoptosis in human leukemia cells by MCS-C2 via caspase-dependent Bid cleavage and cytochrome c relaese

Title
Induction of apoptosis in human leukemia cells by MCS-C2 via caspase-dependent Bid cleavage and cytochrome c relaese
Author
이철훈
Keywords
MCS-C2; leukemia cell; cytochrome c; apoptosis; bid
Issue Date
2005-06
Publisher
ELSEVIER SCI IRELAND LTD
Citation
CANCER LETTERS, v. 223, No. 2, Page. 239-247
Abstract
The purpose of the present study was to investigate the anti-proliferative and apoptotic effects of MCS-C2, a novel synthetic analogue of the pyrrolo[2,3-d]pyrimidine nucleoside toyocamycin and sangivamycin, in human promyelocytic leukemia (HL-60) cells. When treated with 5 mu M MCS-C2, inhibited proliferation associated with apoptotic induction was found in the HL-60 cells in a concentration-dependent and time-dependent manner, plus nuclear DAPI staining revealed the typical nuclear features of apoptosis. However, MCS-C2 showed almost no antiproliferative effect and no apoptotic induction in normal lymphocyte cells used as a control when compared with those in HL-60 cancer cells. Moreover, a flow cytometric analysis of the HL-60 cells using FITC-dUTP and propidium iodide (PI) showed that the apoptotic cell population increased gradually from < 1% at 0 h to 34% at 12 h after exposure to 5 mu M MCS-C2. This apoptotic induction was associated with the cleavage of Bid and a release of cytochrome c from mitochondria into the cytosol, followed by the activation of caspase-3 and inactivation of poly(ADP-ribose) polymerase (PARP). However, there was no significant change in any other mitochondrial membrane proteins, such as Bcl-2 and Bax. Consequently, the current findings suggest that the mitochondrial pathway was primarily involved in the MCS-C2-induced apoptosis in the human promyelocytic leukemia HL-60 cells. (c) 2004 Elsevier Ireland Ltd. All rights reserved.
URI
https://www.sciencedirect.com/science/article/pii/S0304383504008547http://repository.hanyang.ac.kr/handle/20.500.11754/110887
ISSN
0304-3835; 1872-7980
DOI
10.1016/j.canlet.2004.10.045
Appears in Collections:
COLLEGE OF PHARMACY[E](약학대학) > PHARMACY(약학과) > Articles
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