A pharmacologic target of G3139 in melanoma cells may be the mitochondrial VDAC.

Proceedings of the National Academy of Sciences of the United States of America
Johnathan C LaiC A Stein

Abstract

G3139, an 18-mer phosphorothioate antisense oligonucleotide targeted to the initiation codon region of the Bcl-2 mRNA, can induce caspase-dependent apoptosis via the intrinsic mitochondrial pathway in 518A2 and other melanoma cells. G3139-mediated apoptosis appears to be independent of its ability to down-regulate the expression of Bcl-2 protein, because the release of mitochondrial cytochrome c precedes in time the down-regulation of Bcl-2 protein expression. In this study, we demonstrate the ability of G3139 and other phosphorothioate oligonucleotides to bind directly to mitochondria isolated from 518A2 cells. Furthermore, we show that this interaction leads to the release of cytochrome c in the absence of a mitochondrial membrane permeability transition. Our data further demonstrate that there is an interaction between G3139 and VDAC, a protein that can facilitate the physiologic exchange of ATP and ADP across the outer mitochondrial membrane. Evidence from the electrophysiologic evaluation of VDAC channels reconstituted into phospholipid membranes demonstrates that G3139 is capable of producing greatly diminished channel conductance, indicating a closed state of the VDAC. This effect is oligomer length-dependent, and the ab...Continue Reading

References

Jul 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·P S Mangan, M Colombini
Dec 11, 1987·Biochimica Et Biophysica Acta·M ColombiniT König
Jan 1, 1987·Methods in Enzymology·M Colombini
Apr 1, 1997·Nature Medicine·L BenimetskayaC A Stein
Jun 10, 1997·Proceedings of the National Academy of Sciences of the United States of America·P RockwellC A Stein
Jun 1, 1997·The Journal of Membrane Biology·T Hodge, M Colombini
Dec 9, 1997·Cell·G S Salvesen, V M Dixit
Feb 14, 1998·Nature Medicine·B JansenH Pehamberger
Apr 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·M G Vander HeidenC B Thompson
Jan 31, 2002·Proceedings of the National Academy of Sciences of the United States of America·Martin OttSten Orrenius
May 15, 2002·The Journal of Biological Chemistry·Leah J SiskindMarco Colombini
Aug 7, 2002·Antisense & Nucleic Acid Drug Development·Richard J KlasaStanley R Frankel
Dec 17, 2002·Oncogene·Klaus-Michael DebatinGuido Kroemer
Jan 20, 2004·The Journal of Biological Chemistry·Tatiana K RostovtsevaSergey M Bezrukov
May 8, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Anthony RaffoLuba Benimetskaya
Jun 3, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Luba BenimetskayaVolker Gekeler
Dec 30, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Luba BenimetskayaCy A Stein
Aug 12, 2005·Molecular Cancer Therapeutics·Carolyn CaoBo Lu

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Citations

Jul 26, 2008·Journal of Bioenergetics and Biomembranes·C A Stein, Marco Colombini
Jul 26, 2008·Journal of Bioenergetics and Biomembranes·Tatiana K Rostovtseva, Sergey M Bezrukov
Aug 16, 2008·Journal of Bioenergetics and Biomembranes·Eriko SimamuraKei-Ichi Hirai
Apr 10, 2007·Nature Cell Biology·Christopher P BainesJeffery D Molkentin
Jan 20, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Johnathan C LaiCy A Stein
Sep 30, 2006·Annual Review of Physiology·Elizabeth Murphy, Charles Steenbergen
Jun 6, 2007·Future Oncology·Ahmad A Tarhini, John M Kirkwood
Feb 25, 2010·FEBS Letters·Pablo M PeixotoKathleen W Kinnally
Mar 30, 2010·Molecular Aspects of Medicine·Varda Shoshan-BarmatzNir Arbel
Jan 2, 2010·Prostaglandins & Other Lipid Mediators·Sun-Young LeeHo-Shik Kim
Feb 1, 2008·Journal of Controlled Release : Official Journal of the Controlled Release Society·Lavinia LiguoriJean-Luc Lenormand
Apr 19, 2007·Journal of Molecular Biology·Rui Pedro GonçalvesSimon Scheuring
Apr 3, 2007·Journal of Controlled Release : Official Journal of the Controlled Release Society·Hong ZhaoC A Stein
Nov 21, 2015·Saudi Journal of Biological Sciences·Majdouline Abou-Ghali, Johnny Stiban
Apr 8, 2014·Biochimica Et Biophysica Acta·Shira WeisthalVarda Shoshan-Barmatz
Dec 3, 2014·Biochimica Et Biophysica Acta·Varda Shoshan-BarmatzShambhoo Sharan Tripathi
Oct 5, 2010·Biochimica Et Biophysica Acta·Kathleen W KinnallyLaurent M Dejean
May 3, 2011·Mitochondrion·Varda Shoshan-Barmatz, Danya Ben-Hail
Sep 17, 2008·Research in Microbiology·Reiko Ikeda, Kanako Sawamura
Feb 18, 2015·Biochemical and Biophysical Research Communications·C BerrierA Ghazi
Feb 11, 2010·Biochimica Et Biophysica Acta·Hanna GalganskaHanna Kmita
Jun 21, 2014·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Ibrahim AlkatoutBence Sipos
Jun 13, 2016·European Biophysics Journal : EBJ·Roberta PeruzzoLuigi Leanza
May 8, 2007·Biophysical Journal·Wenzhi TanMarco Colombini
Oct 6, 2010·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·A O SantosJ N Moreira
Nov 1, 2007·Organic & Biomolecular Chemistry·Joanne BentleyRichard Cosstick
Jun 15, 2010·ChemMedChem·Johannes WinklerChristian R Noe
May 4, 2007·American Journal of Physiology. Cell Physiology·Roberto ScatenaBruno Giardina
Sep 5, 2014·Current Opinion in Oncology·Daniela Castanotto, Cy A Stein
Sep 13, 2007·The Journal of Clinical Endocrinology and Metabolism·Constantine S MitsiadesNicholas Mitsiades
Aug 9, 2015·The Journal of Biological Chemistry·Li HuangQuan Chen
Jul 18, 2017·Frontiers in Physiology·Amadou K S CamaraWai-Meng Kwok
Sep 13, 2012·Experimental and Therapeutic Medicine·Xu JianZhi Yao
Jul 18, 2018·International Journal of Molecular Sciences·Magdalena BachmannLuigi Leanza
Dec 1, 2006·American Journal of Physiology. Cell Physiology·Wenzhi TanMarco Colombini
Aug 22, 2017·Frontiers in Oncology·Varda Shoshan-BarmatzTasleem Arif
Apr 24, 2018·Frontiers in Chemistry·Andrea MagrìVito De Pinto
Sep 2, 2014·International Journal of Oncology·Asmarinah AsmarinahElvira Hinsch
Aug 18, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Luba BenimetskayaC A Stein

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