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

T. V. Achenbach, E. P. Slater, H. Brummerhop, T. Bach, R. Muller

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

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; ~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.

Original languageEnglish
Pages (from-to)2794-2801
Number of pages8
JournalAntimicrobial Agents and Chemotherapy
Volume44
Issue number10
DOIs
StatePublished - 2000
Externally publishedYes

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