The small organic compound HA14-1 prevents Bcl-2 interaction with Bax to sensitize malignant glioma cells to induction of cell death

Cancer Research
Florence ManeroPhilippe Juin

Abstract

A functional imbalance between proapoptotic Bax and antiapoptotic Bcl-2 is likely to participate in the resistance of cancer cells to therapy. We show here that ethyl 2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate (HA14-1), a small organic compound recently proposed to function as an inhibitor of Bcl-2, increases the sensitivity of human glioblastoma cells to radiotherapy and chemotherapy. This sensitizing effect is lost if Bcl-2 expression, but not Bcl-xL expression, is knocked down or if cells only express a mutant of Bax that does not interact with Bcl-2. This points to a specific Bcl-2 inhibitory function of HA14-1 and implies that it selectively involves hindrance of Bcl-2 binding to Bax, which HA14-1 inhibits in cell-free assays and in cells in receipt of an apoptotic stimulation. Moreover, HA14-1, in combination with a cytotoxic treatment, slows down the growth of glioblastoma in vivo. Thus, the inhibition of Bcl-2 achieved by HA14-1 might improve treatment outcome.

References

Jul 1, 1993·Brain Pathology·P KleihuesB W Scheithauer
May 23, 1997·The Journal of Biological Chemistry·Y T Hsu, R J Youle
Jan 1, 1996·Acta Oncologica·H Blomgren
Jul 4, 1997·The Journal of Biological Chemistry·S OttilieL C Fritz
May 26, 1999·The Journal of Pathology·C A Schmitt, S W Lowe
Jun 22, 2000·Proceedings of the National Academy of Sciences of the United States of America·J L WangZ Huang
Aug 18, 2001·Journal of Neuro-oncology·S MartinF M Vallette
Aug 9, 2002·Molecular and Cellular Biology·Philippe JuinGerard Evan
Sep 10, 2002·Chemotherapy·Patrick GuensbergBurkhard Jansen
Jan 17, 2003·The Journal of Biological Chemistry·Pierre-François CartronFrançois M Vallette
Feb 1, 2003·Lancet·Anthony BehinJean-Yves Delattre
Mar 19, 2003·The Journal of Biological Chemistry·Carole MoreauPhilippe Juin
Apr 3, 2003·Genes & Development·Ming Jiang, Jo Milner
Jun 17, 2003·Molecular and Cellular Biology·Pierre-François CartronFrançois M Vallette
Dec 19, 2003·The Journal of Biological Chemistry·Pierre-François CartronFrançois M Vallette
Mar 5, 2004·Biochimica Et Biophysica Acta·Andrew M PetrosStephen W Fesik
Mar 5, 2004·Biochimica Et Biophysica Acta·Philippe JuinJohn A Hickman
May 8, 2004·The EMBO Journal·Seon-Yong JeongRichard J Youle
Dec 14, 2004·The Journal of Biological Chemistry·Pierre-François CartronFrançois M Vallette
Apr 23, 2005·Cell Cycle·Philippe JuinFrançois M Vallette
May 20, 2005·Nature·Tilman OltersdorfSaul H Rosenberg
Oct 26, 2005·Current Opinion in Cell Biology·Simon N Willis, Jerry M Adams

❮ Previous
Next ❯

Citations

Oct 6, 2011·Pediatric Surgery International·Justus LieberSorin Armeanu-Ebinger
Jun 22, 2010·Apoptosis : an International Journal on Programmed Cell Death·Joanna SkommerSubhadip Raychaudhuri
Apr 25, 2012·Journal of Molecular Neuroscience : MN·Shuguang ZhangLei Shi
May 15, 2010·Nature Reviews. Drug Discovery·Simone FuldaGuido Kroemer
Jan 9, 2008·Photochemistry and Photobiology·David Kessel
Jun 30, 2009·Molecular Pharmacology·David HermansonChengguo Xing
Dec 22, 2010·Molecular and Cellular Biology·F GautierP Juin
Feb 21, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Min H Kang, C Patrick Reynolds
Sep 9, 2011·Genes & Cancer·Rana ElkholiJerry E Chipuk
Sep 2, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Benjamin D ZeitlinJacques E Nör
May 24, 2011·World Journal of Clinical Oncology·Subhadip Raychaudhuri
Mar 21, 2012·TheScientificWorldJournal·Fotini M KouriAlexander H Stegh
Nov 24, 2012·Expert Opinion on Therapeutic Targets·Shibu ThomasPaul B Fisher
May 6, 2015·Seminars in Cancer Biology·Ramzi M MohammadAsfar S Azmi
Apr 22, 2009·The Journal of Cell Biology·Tristan GallennePhilippe Juin
Feb 19, 2015·International Journal of Molecular Sciences·Justus LieberJörg Fuchs
Sep 4, 2010·Expert Opinion on Emerging Drugs·Asfar S AzmiFazlul H Sarkar
Mar 25, 2015·Artificial Cells, Nanomedicine, and Biotechnology·Hitesh JaganiVenkata Rao Josyula
Nov 7, 2015·Journal of Neuro-oncology·Jeffrey WojtonBalveen Kaur
Mar 19, 2013·Journal of Healthcare Engineering·Subhadip Raychaudhuri, Somkanya C Das
Dec 9, 2010·Journal of Controlled Release : Official Journal of the Controlled Release Society·M WeylandE Garcion
Aug 25, 2009·Molecular Aspects of Medicine·Lorenzo GalluzziGuido Kroemer
Jan 7, 2009·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Cheng-Yun JinYung Hyun Choi
Sep 9, 2008·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·Nobuyuki HamadaYasuhiko Kobayashi
Nov 13, 2015·Molecular Pharmaceutics·Jeyarama S AnantaTarik F Massoud
Oct 9, 2007·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Lin ZhangJian Yu
Dec 13, 2006·Neurobiology of Disease·Cornelia FrankeGunter P Eckert
Mar 10, 2010·Environmental and Molecular Mutagenesis·David M Hockenbery
Oct 15, 2013·Chemical Biology & Drug Design·Kanwal RehmanMehmood H Qazi
Apr 2, 2011·Biochimica Et Biophysica Acta·Inthrani R IndranCatherine Brenner

❮ Previous
Next ❯

Related Concepts

Related Feeds

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.