Staurosporine and conventional anticancer drugs induce overlapping, yet distinct pathways of apoptosis and caspase activation

Oncogene
A StepczynskaK Schulze-Osthoff

Abstract

Apoptosis can be induced by various stimuli including DNA-damaging anticancer drugs and the protein kinase inhibitor staurosporine. It is generally believed that the molecular events during execution of apoptosis are shared, as both anticancer drugs and staurosporine derivatives induce mitochondrial damage, cytochrome c release and the activation of the caspase-9 proteolytic cascade. In the present study we show that overexpression of a dominant-negative caspase-9 mutant abolished the activation of endogenous caspase-9, caspase-3 and the cleavage of the caspase substrate Bid in response to anticancer drug treatment. Surprisingly, however, only marginal effects were observed during staurosporine-induced apoptosis. Furthermore, we describe a Jurkat T-cell clone that is completely resistant towards different anticancer drugs, but remains sensitive towards staurosporine-induced apoptosis. In these cells only staurosporine, but neither anti-CD95 nor anticancer drugs were able to trigger caspase activity and the cleavage of caspase substrates. Our results therefore suggest that the mechanism of staurosporine-induced apoptosis is more complex and at least partially differs from anticancer drug-induced caspase activation. These distinc...Continue Reading

References

Feb 15, 1990·The Biochemical Journal·S A RotenbergI B Weinstein
Jun 1, 1989·Trends in Pharmacological Sciences·U T Rüegg, G M Burgess
Oct 1, 1994·The Journal of Cell Biology·K Schulze-OsthoffP H Krammer
Apr 1, 1994·Experimental Cell Research·R BertrandY Pommier
Jan 1, 1993·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·M C PagliacciI Nicoletti
Jun 1, 1996·The Journal of Cell Biology·M D JacobsenM C Raff
Aug 15, 1997·The Biochemical Journal·G M Cohen
May 2, 1998·The EMBO Journal·C ScaffidiM E Peter
Jun 17, 1998·Genes & Development·V Cryns, J Yuan
Aug 4, 1998·European Journal of Biochemistry·K Schulze-OsthoffM E Peter
Oct 24, 1998·European Journal of Anaesthesiology·S GuptaD Niblett
Nov 11, 1998·General Pharmacology·A Gescher
Nov 13, 1998·Science·M H CardoneJ C Reed
Jul 31, 1999·The Journal of Biological Chemistry·C ScaffidiM E Peter
Sep 22, 1999·European Journal of Biochemistry·S MasureA Richardson
Oct 26, 1999·Biochemical and Biophysical Research Communications·E FujitaT Momoi
Dec 22, 1999·Oncogene·M Barkett, T D Gilmore
Jan 11, 2000·Molecular and Cellular Biology·R EskesJ C Martinou
May 17, 2000·The Journal of Experimental Medicine·M HaraguchiJ C Reed

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Citations

Dec 7, 2007·Apoptosis : an International Journal on Programmed Cell Death·Christoph Peter BergKirsten Lauber
Feb 11, 2010·Apoptosis : an International Journal on Programmed Cell Death·Anirudh J Ullal, David S Pisetsky
Mar 18, 2003·Cellular Signalling·Brian C Oxhorn, Iain L O Buxton
Feb 5, 2003·Drug Discovery Today·Marek LosAndrzej Mackiewicz
Jan 31, 2009·Cell Death and Differentiation·M CzystowskaT L Whiteside
Dec 1, 2012·Cell Death and Differentiation·T Imao, S Nagata
Mar 7, 2002·The Biochemical Journal·Christopher J DoughertyKeith A Webster
May 12, 2011·The Journal of Biological Chemistry·Samantha B NichollsJeanne A Hardy
Feb 22, 2011·Omics : a Journal of Integrative Biology·Anna HalamaJerzy Adamski
Oct 5, 2007·Journal of Virology·Sungyong WonShinji Makino
Oct 10, 2007·Molecular and Cellular Biology·Timothée RevilBenoit Chabot
Nov 23, 2005·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Valentina YurinskayaAlexey Vereninov
Dec 3, 2009·Virology Journal·Christoph P BergGerburg M Stein
Feb 16, 2013·Radiology and Oncology·Janez Simenc, Metoda Lipnik-Stangelj
Aug 17, 2010·Indian Journal of Pharmacology·Pathirage Kamal PereraCaifeng Han
Jun 12, 2002·Cell Death and Differentiation·H KashkarJ M Jürgensmeier
Sep 21, 2012·Chemical Communications : Chem Comm·Kyoungsook ParkBong Hyun Chung
Mar 1, 2012·Drug and Chemical Toxicology·Janez Šimenc, Metoda Lipnik-Štangelj
Aug 24, 2013·Expert Opinion on Drug Discovery·Patricia McGrath, Wen Lin Seng
Jul 9, 2004·Scandinavian Journal of Immunology·J-J ChoiD S Pisetsky
Jan 6, 2009·Journal of Cellular and Molecular Medicine·David J HookerCatherine L Cherry
Jan 13, 2006·Angewandte Chemie·Peter T DanielJulia Schuppan
Mar 25, 2010·Journal of Cellular Physiology·Lingling ZhangDa Xing
Aug 2, 2002·Biochemical and Biophysical Research Communications·Jürgen BockErich Gulbins
Jul 23, 2015·Journal of Experimental & Clinical Cancer Research : CR·Martina Broecker-PreussKlaus Mann
Apr 20, 2006·Biochemical Pharmacology·Federico CusinatoLucia Trevisi
Apr 3, 2016·Journal of Cancer Research and Clinical Oncology·Regina MaushagenBarbara Wollenberg
Apr 10, 2016·Microscopy Research and Technique·Sara SalucciElisabetta Falcieri

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