Involvement of Akt in mitochondria-dependent apoptosis induced by a cdc25 phosphatase inhibitor naphthoquinone analog
- Authors
- Kim, HJ; Kang, SK; Mun, JY; Chun, YJ; Choi, KH; Kim, MY
- Issue Date
- Dec-2003
- Publisher
- ELSEVIER SCIENCE BV
- Keywords
- naphthoquinone analog; apoptosis; cytochrome c; Bad; Akt
- Citation
- FEBS LETTERS, v.555, no.2, pp 217 - 222
- Pages
- 6
- Journal Title
- FEBS LETTERS
- Volume
- 555
- Number
- 2
- Start Page
- 217
- End Page
- 222
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/24912
- DOI
- 10.1016/S0014-5793(03)01238-9
- ISSN
- 0014-5793
1873-3468
- Abstract
- Vitamin K-related analogs induce growth inhibition via a cell cycle arrest through cdc25A phosphatase inhibition in various cancer cell tines. We report that 2,3-dichloro-5,8-dihydroxy-1,4-naphthoquinone (DDN), a naphthoquinone analog, induces mitochondria-dependent apoptosis in human promyelocytic leukemia HL-60 cells. DDN induced cytochrome c release, Bax translocation, cleavage of Bid and Bad, and activation of caspase-3, -8, -9 upon the induction of apoptosis. Cleavage of Bid, the caspase-8 substrate, was inhibited by the broad caspase inhibitor z-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD-fmk), whereas cytochrome c release was not affected, suggesting that activation of caspase-8 and subsequent Bid cleavage occur downstream of cytochrome c release. DDN inhibited the activation of Akt detected by decreasing level of phosphorylation. Overexpression of constitutively active Akt protected cells from DDN-induced apoptosis, while dominant negative Akt moderately enhanced cell death. Furthermore, Akt prevented release of cytochrome c and cleavage of Bad in DDN-treated HL-60 cells. Taken together, DDN-induced apoptosis is associated with mitochondrial signaling which involves cytochrome c release via a mechanism inhibited by Akt. (C) 2003 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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