Induction of apoptosis in human leukemia cells by MCS-C2 via caspase-dependent Bid cleavage and cytochrome c release
- Authors
- Kim, Min Kyoung; Cho, Youl-Hee; Kim, Jung Mogg; Moon Woo Chun; Lee, Seung Ki; Lim, Yoongho; Lee, Chul-Hoon
- Issue Date
- Jun-2005
- Publisher
- Elsevier BV
- Keywords
- MCS-C2; leukemia cell; cytochrome c; apoptosis; bid
- Citation
- Cancer Letters, v.223, no.2, pp 239 - 247
- Pages
- 9
- Indexed
- SCIE
SCOPUS
- Journal Title
- Cancer Letters
- Volume
- 223
- Number
- 2
- Start Page
- 239
- End Page
- 247
- URI
- https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/45872
- DOI
- 10.1016/j.canlet.2004.10.045
- ISSN
- 0304-3835
1872-7980
- 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.
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