title: Cell cycle-independent induction of apoptosis by the anti-tumor drug Flavopiridol in endothelial cells.
abstract: The anti-tumor drug Flavopiridol is a potent inhibitor of cyclin-dependent kinases (cdks). As a consequence, Flavopiridol-treated cells arrest in both G1 and G2, but Flavopiridol has also been shown to be cytotoxic for some tumor cell lines. The underlying molecular events are, however, unclear. We now show that Flavopiridol induces apoptosis in human umbilical vein endothelial cells (HUVECs), as judged by the occurrence of classical apoptotic markers, including chromatin condensation, internucleosomal cleavage, DNA fragmentation (TUNEL assay), annexin V binding and poly(ADP-ribose) polymerase (PARP)-cleavage. Such induction of apoptosis occurs with equal efficiency in both proliferating and G0/G1-arrested cells. Because growth-arrested HUVECs lack cdk2 activity and contain high levels of the cdk inhibitor p27, our observations suggest that cell cycle regulated cdks may not be the only critical target for Flavopiridol-induced apoptosis. Surprisingly, A549 lung carcinoma cells were clearly dependent on cell proliferation for the induction of cell death, pointing to cell type-related differences in the mechanism of Flavopiridol action.
authors.affiliation: Institut für Molekularbiologie und Tumorforschung, Philipps-Universität Marburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Brüsselbach
authors.forename: D M
authors.initials: DM
authors.lastname: Nettelbeck
authors.forename: H H
authors.initials: HH
authors.lastname: Sedlacek
authors.forename: R
authors.initials: R
authors.lastname: Müller
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology*; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D010880:Piperidines / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D005419:Flavonoids; D010880:Piperidines; C077990:alvocidib