Mcl-1 antisense therapy chemosensitizes human melanoma in a SCID mouse xenotransplantation model

The Journal of Investigative Dermatology
Christiane ThallingerBurkhard Jansen

Abstract

It is well established that high expression of the antiapoptotic Bcl-2 family proteins Bcl-2 and Bcl-xL can significantly contribute to chemoresistance in a number of human malignancies. Much less is known about the role the more recently described Bcl-2 family member Mcl-1 might play in tumor biology and resistance to chemotherapy. Using an antisense strategy, we here address this issue in melanoma, a paradigm of a treatment-resistant malignancy. After in vitro proof of principle supporting an antisense mechanism of action with specific reduction of Mcl-1 protein as a consequence of nuclear uptake of the Mcl-1 antisense oligonucleotides employed, antisense and universal control oligonucleotides were administered systemically in combination with dacarbazine in a human melanoma SCID mouse xenotransplantation model. Dacarbazine, available now for more than three decades, still remains the most active single agent for treatment of advanced melanoma. Mcl-1 antisense oligonucleotides specifically reduced target protein expression as well as the apoptotic threshold of melanoma xenotransplants. Combined Mcl-1 antisense oligonucleotide plus dacarbazine treatment resulted in enhanced tumor cell apoptosis and led to a significantly reduc...Continue Reading

References

Dec 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·J M LehmannJ P Johnson
Apr 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·K M KozopasR W Craig
Nov 4, 1994·Science·S W LoweT Jacks
Mar 1, 1993·Immunology Today·J J Cohen
Apr 19, 1997·Lancet·A WebbZ Dziewanowska
Feb 14, 1998·Nature Medicine·B JansenH Pehamberger
May 23, 1998·Annual Review of Immunology·D T Chao, S J Korsmeyer
Feb 13, 1999·Cell·D L Vaux, S J Korsmeyer
May 25, 1999·Melanoma Research·L Serrone, P Hersey
Aug 18, 1999·Proceedings of the National Academy of Sciences of the United States of America·K MoriishiJ M Adams
Dec 1, 1999·Endocrinology·A L Johnson
Jan 19, 2000·Trends in Pharmacological Sciences·K J Myers, N M Dean
Oct 19, 2000·Cancer Investigation·B P MoniaF A Dorr
Dec 29, 2000·Cellular and Molecular Life Sciences : CMLS·C AkgulS W Edwards
Mar 30, 2001·The Journal of Biological Chemistry·D D BannermanJ M Harlan
Mar 30, 2001·Cell Death and Differentiation·S ConusC Borner
Nov 3, 2001·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·V WacheckB Jansen
Mar 5, 2002·The Journal of Investigative Dermatology·Robert A OlieUwe Zangemeister-Wittke
Mar 21, 2002·Expert Opinion on Therapeutic Targets·Guy Makin
Apr 12, 2002·International Journal of Cancer. Journal International Du Cancer·Elisabeth Heere-RessBurkhard Jansen
Sep 28, 2002·Blood·Irene M PedersenJohn C Reed
Nov 9, 2002·The Lancet Oncology·Burkhard Jansen, Uwe Zangemeister-Wittke

❮ Previous
Next ❯

Citations

Mar 27, 2007·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Liqing ZhuangPeter Hersey
Aug 9, 2012·Antioxidants & Redox Signaling·Balachandran S VinodRuby John Anto
May 6, 2004·Journal of the National Cancer Institute·Shinichi Kitada, John C Reed
Jul 22, 2010·Cancer Research·Yongping Shao, Andrew E Aplin
Apr 18, 2009·Molecular Cancer Research : MCR·Karen Boisvert-AdamoAndrew E Aplin
Apr 28, 2012·Molecular Cancer·Aitziber BuquéGuillermo López-Vivanco
Sep 1, 2007·Cancer Research and Treatment : Official Journal of Korean Cancer Association·Jong-Soo Lee
Aug 20, 2011·Expert Opinion on Investigational Drugs·Bridget A QuinnPaul B Fisher
Jan 24, 2013·Cancer Letters·Mariusz L Hartman, Malgorzata Czyz
Feb 7, 2012·Journal of Dermatological Science·Shi-Wei HuangJeng-Jer Shieh
Aug 31, 2014·Pharmacology & Therapeutics·Johannes Belmar, Stephen W Fesik
Jan 6, 2012·The Journal of Investigative Dermatology·Vasiliki A NikolaouHensin Tsao
Dec 17, 2008·The Journal of Investigative Dermatology·Tobias SinnbergFriedegund Meier
Mar 8, 2008·The Journal of Investigative Dermatology·Konstantinos G LasithiotakisFriedegund E Meier
Mar 28, 2008·The Journal of Investigative Dermatology·Hossain M Najar, Jan P Dutz
Mar 11, 2006·The Journal of Investigative Dermatology·Lothar F FeckerJürgen Eberle
Oct 18, 2008·The Journal of Investigative Dermatology·Thomas L HockerHensin Tsao
Dec 7, 2007·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Jürgen EberleLothar F Fecker
Oct 2, 2007·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Tik-Shun HoVincent Eng-Choon Ooi
Jul 8, 2009·Journal of Surgical Oncology·Wang LikuiLi Xiaojun
Dec 9, 2004·Biochimica Et Biophysica Acta·Jeff CummingsCaroline Dive
Jul 22, 2008·Biochemical Pharmacology·Isabel Marzo, Javier Naval
Nov 18, 2005·Journal of Hepatology·Wolfgang SieghartVolker Wacheck
Feb 15, 2007·Expert Opinion on Therapeutic Targets·Arthur M Mandelin, Richard M Pope
Jun 17, 2015·BioMed Research International·Chunlin JiangMing Kuang
Dec 9, 2014·Experimental Cell Research·Michele ModugnoArturo Galvani
Aug 31, 2006·International Review of Cytology·Peter HerseyX D Zhang
Oct 18, 2016·Expert Opinion on Therapeutic Patents·Lijia Chen, Steven Fletcher
Dec 10, 2003·Oncogene·Nicholas M Dean, C Frank Bennett
Aug 12, 2004·British Journal of Cancer·D L DaiG Li
Mar 21, 2006·Apoptosis : an International Journal on Programmed Cell Death·E MinetC Michiels
Feb 27, 2014·Asian Pacific Journal of Cancer Prevention : APJCP·Hadi KaramiEbrahim Sakhinia
Aug 15, 2019·Fundamental & Clinical Pharmacology·Michalina RespondekDorota Wrześniok
Mar 12, 2004·The Journal of Biological Chemistry·Jie HanHannah Rabinowich
May 18, 2017·Cancer Biology & Therapy·Fade MahmoudAlan J Tackett

❮ Previous
Next ❯

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