Complestatin prevents apoptotic cell death: Inhibition of a mitochondrial caspase pathway through AKT/PKB activation

Eok Cheon Kim, Bong Sik Yun, In Ja Ryoo, Jeong Ki Min, Moo Ho Won, Kwang Soon Lee, Young Myeong Kim, Ick Dong Yoo, Young Guen Kwon

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)


Complestatin, a bicyclo hexapeptide from Streptomyces, was isolated as a possible regulator of neuronal cell death. In this study, we report an anti-apoptotic activity of complestatin and its underlying molecular mechanism. Complestatin blocked TRAIL (TNF-related apoptosis-inducing ligand)-induced apoptosis and activation of caspase-3 and -8 at micromolar concentration levels without inhibiting the catalytic activities of these caspases. Complestatin potently induced a rapid and sustained AKT/PKB activation and Bad phosphorylation, resulting in inhibition of mitochondrial cytochrome c release. These anti-apoptotic activities of complestatin were significantly abrogated in cells expressing dominant negative AKT/PKB. Taken together, our results suggest that complestatin prevents apoptotic cell death via AKT/PKB-dependent inhibition of the mitochondrial apoptosis signal pathway. The novel property of complestatin may be valuable for developing new pharmaceutical means that will control unwanted cell death.

Original languageEnglish
Pages (from-to)193-204
Number of pages12
JournalBiochemical and Biophysical Research Communications
Issue number1
Publication statusPublished - 2004 Jan 2

Bibliographical note

Funding Information:
We extend our sincere thanks to Dr. Timothy R. Billiar (University of Pittsburgh) for providing HA-AKT and DN-AKT expression vector. We thank Dr. James A. Bibb (University of Texas Southwestern) for critical reading of the manuscript. This work was supported by G7 and NRL grants (to I.-D.Y.) and a Vascular System Research Center grant (to Y.-G.K.), Ministry of Science and Technology, Republic of Korea.

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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