The BH3-only member Noxa causes apoptosis in melanoma cells by multiple pathways

Oncogene
M HassanU R Hengge

Abstract

The molecular causes for resistance of melanoma to apoptosis are currently only partly understood. In the present study, we examined gene transfer and expression of the proapoptotic BH3-only protein Noxa as an alternative approach to chemotherapy and investigated the molecular mechanisms regulating Noxa-induced apoptosis. Noxa gene transfer caused dysregulation of both mitochondria and, as shown for the first time, also the endoplasmic reticulum, resulting in the accumulation of reactive oxygen species. Interestingly, expression of Noxa not only triggered the classical mitochondrial caspase cascade, but also resulted in the activation of apoptosis signal-regulating kinase1 and its downstream effectors c-Jun N-terminal kinase and p38. The activation of these kinases was abolished by antioxidants. Moreover, inhibition of the kinases by RNA interference or pharmacological inhibitors significantly attenuated Noxa-induced apoptosis. Thus, our data provide evidence for the involvement of multiple pathways in Noxa-induced apoptosis that are triggered at mitochondria and the endoplasmic reticulum, and suggest Noxa gene transfer as a complementary approach to chemotherapy.

References

Aug 26, 1998·Biochimica Et Biophysica Acta·J CaiD P Jones
Aug 16, 2001·Trends in Biochemical Sciences·A S Lee
Jun 6, 2003·Oncogene·María S Soengas, Scott W Lowe
Jul 9, 2003·The Journal of Cell Biology·Wei-Xing ZongCraig B Thompson
Jul 24, 2003·The Journal of Biological Chemistry·Abel C S Chun, Dong-Yan Jin
Sep 4, 2003·Genes & Development·Tsukasa ShibueNobuyuki Tanaka
Oct 31, 2003·Essays in Biochemistry·Peter T DanielDilek Güner
Dec 12, 2003·Nature Reviews. Cancer·Robert Eferl, Erwin F Wagner
Dec 20, 2003·The Journal of Biological Chemistry·Tzippi Hershko, Doron Ginsberg
Dec 31, 2003·The Journal of Experimental Medicine·Jee-Youn KimJae-Hoon Park
Aug 11, 2005·Cellular and Molecular Life Sciences : CMLS·M HassanU R Hengge
Sep 9, 2005·The Journal of Biological Chemistry·Frank EssmannReiner U Jänicke
Apr 29, 2006·Cell Death and Differentiation·V LabiA Villunger
Oct 5, 2006·Cancer Research·Jian-Zhong QinBrian J Nickoloff

❮ Previous
Next ❯

Citations

Apr 9, 2013·Apoptosis : an International Journal on Programmed Cell Death·Denis SelimovicMohamed Hassan
Jul 15, 2009·Biological Procedures Online·Adria D DismukeMelissa H Wong
Sep 15, 2011·Pigment Cell & Melanoma Research·Pablo Lopez-Bergami
Jan 24, 2006·BMC Cell Biology·Carrie FathkeFrank Isik
Dec 24, 2010·BMC Developmental Biology·Anna Ferrer-VaquerAnna-Katerina Hadjantonakis
Mar 17, 2006·BMC Developmental Biology·Leigh-Anne D MillerRichard A Lang
Aug 1, 2008·BMC Genomics·Salih S KoçerMaja Matic
Dec 6, 2008·BMC Gastroenterology·Paige S DaviesMelissa H Wong
Mar 29, 2008·Breast Cancer Research : BCR·Alastair ThompsonCharles Streuli
Jun 10, 2004·Journal of Biology·Tadashi Okubo, Brigid L M Hogan
Apr 11, 2009·PloS One·Olga VareaFrancisco Wandosell
May 19, 2009·Expert Review of Anticancer Therapy·Ryan J Sullivan, Michael B Atkins
Aug 7, 2010·Expert Opinion on Investigational Drugs·Ryan J Sullivan, Michael B Atkins
Nov 19, 2015·Journal of Cellular and Molecular Medicine·Abdelouahid El-KhattoutiMohamed Hassan
Jan 28, 2012·Cancer Letters·Kris Nys, Patrizia Agostinis
Aug 17, 2011·Environmental Toxicology and Pharmacology·Sailendra Nath SarmaJae-Chun Ryu
Mar 17, 2010·Biochemical and Biophysical Research Communications·Min YouLynn Feun
Jun 19, 2009·The Journal of Investigative Dermatology·Alireza MirmohammadsadeghUlrich R Hengge
Feb 25, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Mohamed HassanOla Abdel-kader
Jul 22, 2008·Biochemical Pharmacology·Isabel Marzo, Javier Naval
Jul 25, 2015·The Journal of Pharmacy and Pharmacology·Yahima Frión-HerreraJosé Maurício Sforcin
Apr 20, 2012·World Journal of Experimental Medicine·Mohamed HassanOla Abdelkader
Dec 1, 2015·World Journal of Experimental Medicine·Mohamed HassanMossaad Megahed
Jan 1, 2013·Journal of Cell Death·Abdelouahid El-KhattoutiMohamed Hassan
Nov 19, 2014·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Suvasmita RathAsima Bhattacharyya
Nov 20, 2016·Journal of Cellular and Molecular Medicine·Jee-Youn KimJaeho Cho

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptotic Caspases

Apoptotic caspases belong to the protease enzyme family and are known to play an essential role in inflammation and programmed cell death. Here is the latest research.

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