PMID: 9639406Jun 25, 1998Paper

Cell cycle-independent induction of apoptosis by the anti-tumor drug Flavopiridol in endothelial cells

International Journal of Cancer. Journal International Du Cancer
S BrüsselbachR Müller

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.

References

Nov 18, 1992·Journal of the National Cancer Institute·G KaurE Sausville
Jul 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·K SadhuP Russell
Feb 1, 1988·Experimental Cell Research·P S RabinovitchH Hoehn
May 1, 1995·Trends in Genetics : TIG·R Müller
Mar 1, 1994·Molecular and Cellular Biology·H MatsushimeJ Y Kato
Apr 2, 1996·Proceedings of the National Academy of Sciences of the United States of America·W F De AzevedoS H Kim
Jan 1, 1997·Trends in Genetics : TIG·J Zwicker, R Müller

❮ Previous
Next ❯

Citations

Sep 19, 2000·Antimicrobial Agents and Chemotherapy·T V AchenbachR Müller
Feb 8, 2006·DNA and Cell Biology·Kiminori MatsubaraYoshiyuki Mizushina
Jan 28, 2006·Nucleosides, Nucleotides & Nucleic Acids·Jennifer Sigmond, Godfridus J Peters
Mar 16, 2013·Leukemia & Lymphoma·James S Blachly, John C Byrd
Jun 5, 2003·Expert Opinion on Investigational Drugs·Peter M Fischer, Athos Gianella-Borradori
Jul 12, 2005·Expert Opinion on Investigational Drugs·Kenneth KhamlyJohn Zalcberg
Nov 28, 2000·Expert Opinion on Investigational Drugs·L R Kelland
Nov 4, 2000·Expert Opinion on Investigational Drugs·H K Wang
May 31, 2007·Neoplasia : an International Journal for Oncology Research·M Aktar AliDebabrata Saha
Dec 12, 2003·Clinical Lung Cancer·Adrian M Senderowicz
Apr 5, 2016·Seminars in Oncology·James S BlachlyMichael Grever
Aug 30, 2001·Hematology/oncology Clinics of North America·D M Reese
Jan 7, 2003·Hematology/oncology Clinics of North America·Adrian M Senderowicz
Jul 28, 2016·Journal of Cancer Research and Therapeutics·Gozde CobanogluAbdullah Ekmekci
Sep 28, 2002·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Antoinette R TanAdrian M Senderowicz
Oct 7, 2003·Oncogene·Adrian M Senderowicz
May 29, 2004·Anti-cancer Drugs·Elizabeth W Newcomb
Jun 21, 2002·Annals of the New York Academy of Sciences·Kishorchandra Gohil, Lester Packer
Apr 25, 2000·Drugs·H H Sedlacek
Dec 31, 2002·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·G FreyerV Trillet-Lenoir
Jan 19, 2000·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·W M StadlerE E Vokes
Aug 30, 2012·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Marialucia GalloriniViviana di Giacomo
May 9, 2003·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·C Tom KouroukisUNKNOWN National Cancer Institute of Canada Clinical Trials Group
Aug 7, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Antoinette R TanSandra M Swain
Aug 24, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Keith C BibleCharles Erlichman
May 4, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Christina RichardJohn P H Th'ng
Mar 10, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Saltanat NajmiRobert Wieder
Apr 30, 2002·The Annals of Pharmacotherapy·Suoping ZhaiWilliam D Figg
May 23, 2001·Archives of Biochemistry and Biophysics·A KaiserJ B Schnier
Apr 20, 2001·Critical Reviews in Oncology/hematology·H H Sedlacek
May 9, 2000·Critical Reviews in Oncology/hematology·M Hagedorn, A Bikfalvi
Jul 18, 2002·The Journal of Nutritional Biochemistry·Yihai CaoEbba Bråkenhielm
Apr 26, 2003·Bioorganic & Medicinal Chemistry·Norman S Radin
Jun 5, 2007·Critical Reviews in Oncology/hematology·David Michod, Christian Widmann

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.

Cell Cycle Pathways

Cell cycle is a complex process regulated by several signal transduction pathways and enzymes. Here is the latest research on regulation of cell cycle and cell cycle pathways.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis