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

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 microM 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 microM 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.
AuthorsMin Kyoung Kim, Youl-Hee Cho, Jung Mogg Kim, Moon Woo Chun, Seung Ki Lee, Yoongho Lim, Chul-Hoon Lee
JournalCancer letters (Cancer Lett) Vol. 223 Issue 2 Pg. 239-47 (Jun 08 2005) ISSN: 0304-3835 [Print] Ireland
PMID15896458 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • MCS-C2
  • Cytochromes c
  • CASP3 protein, human
  • Caspase 3
  • Caspases
  • Toyocamycin
Topics
  • Apoptosis (drug effects)
  • Caspase 3
  • Caspases (metabolism)
  • Cell Proliferation (drug effects)
  • Cytochromes c (metabolism)
  • HL-60 Cells
  • Humans
  • Kinetics
  • Mitochondria
  • Toyocamycin (analogs & derivatives, pharmacology)

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