Inhibition of cyclin-dependent kinase activity and induction of apoptosis by preussin in human tumor cells.

Abstract

In this paper, we report that (+)-preussin, a pyrrolidinol alkaloid originally identified as an antifungal agent, has growth-inhibitory and cytotoxic effects on human cancer cells. Preussin was found to be a potent inhibitor of cyclin E kinase (CDK2-cyclin E) in vitro (50% inhibitory concentration; approximately 500 nM) and to inhibit cell cycle progression into S phase. In agreement with these findings, the level of the cyclin-dependent kinase inhibitor p27(KIP-1) is increased in response to preussin treatment while the expression of both cyclin A and the transcription factor E2F-1 is down-regulated. Preussin also induces programmed cell death (apoptosis), which requires caspase activation and involves the release of cytochrome c from mitochondria. This induction of apoptosis is not blocked by high levels of Bcl-2, which usually confers resistance to chemotherapeutic agents. Taken together, our data indicate that preussin could be a promising lead compound for the development of a new class of potent antitumor drugs.

Cite this paper

@article{Achenbach2000InhibitionOC, title={Inhibition of cyclin-dependent kinase activity and induction of apoptosis by preussin in human tumor cells.}, author={Tatjana V Achenbach and Emily Prentice Slater and Harm Brummerhop and Trond Bach and Rolf A. E. Mueller}, journal={Antimicrobial agents and chemotherapy}, year={2000}, volume={44 10}, pages={2794-801} }