Involvement of miltefosine-mediated ERK activation in glioma cell apoptosis through Fas regulation

Journal of Neurochemistry
Richa TewariEllora Sen

Abstract

The anti-neoplastic property of alkyl phospholipids has been tested for the treatment of several malignancies. In this study, we evaluated the efficacy of miltefosine (Hexadecylphosphocholine--an alkyl phospholipids analogue) on glioblastoma multiforme. In this study, we demonstrate that miltefosine-induced apoptosis is accompanied by elevated Fas, Fas-associated death domain (FADD) expression, caspase-8 activity and the increased distribution of Fas and FADD towards lipid raft microdomain to form death inducing signaling complex. Treatment with miltefosine resulted in increase in Ras, extracellular signal-regulated kinase (ERK) and p38MAPK activity. Expression of dominant-negative Ras (Ras N17) attenuated miltefosine-mediated apoptosis. Although inhibition of both ERK and p38MAPK decreased the pro-apoptotic effects of miltefosine, it was the inhibition of ERK and not p38MAPK activation that decreased Fas and FADD expression. An ERK-dependent increase in the expression of gammaH2AX-involved in response to DNA double-stranded breaks was also observed. Taken together, our findings suggest the involvement of ERK activation in miltefosine-induced glioma cell apoptosis.

References

Feb 7, 1997·Cell·T Hunter
Mar 1, 1997·Genes & Development·A C LloydH Land
Apr 8, 1998·Current Opinion in Genetics & Development·J Downward
Jun 27, 1998·The Journal of Biological Chemistry·C Y ChenD V Faller
Dec 10, 1998·Cell Death and Differentiation·C Y ChenD V Faller
Jun 8, 1999·Annual Review of Immunology·D WallachM P Boldin
Sep 20, 2000·The Journal of Biological Chemistry·X WangN J Holbrook
Jan 11, 2001·The New England Journal of Medicine·L M DeAngelis
May 19, 2001·The New England Journal of Medicine·R S Ross, M Roggendorf
Aug 30, 2001·Cell·F GalbiatiM P Lisanti
Aug 23, 2003·Oncogene·Heike GrassméErich Gulbins
Apr 17, 2004·Cancer Research·John T StickneyWallace Ip
May 20, 2004·Cancer Research·Sandrine LacourMarie-Thérèse Dimanche-Boitrel
Jun 1, 2005·Biophysical Journal·J Shawn GoodwinAnne K Kenworthy
Jan 11, 2007·Genes & Development·Frédérick A MalletteGerardo Ferbeyre
Sep 19, 2007·Molecular Cancer Therapeutics·Vivek SharmaEllora Sen

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Citations

Nov 17, 2010·PloS One·Diana Aguilar-MoranteAna Perez-Castillo
Sep 10, 2014·Journal of Enzyme Inhibition and Medicinal Chemistry·Ahmet CumaogluNilgun Kalaycioglu Ozpozan
Oct 29, 2015·Journal of Neuroscience Research·Vimal PandeyPhanithi Prakash Babu
Jul 9, 2009·Journal of Cellular and Molecular Medicine·Vivek SharmaEllora Sen
Jul 4, 2012·Molecular Carcinogenesis·Ruchi GhildiyalEllora Sen
Oct 22, 2009·The FEBS Journal·Sebastien Cagnol, Jean-Claude Chambard
Mar 13, 2012·Free Radical Biology & Medicine·Jörn M SchattenbergMarcus Schuchmann
Apr 23, 2009·Molecular Oncology·Richa TewariEllora Sen
Mar 21, 2015·PloS One·Hussein AkilJean-Claude Lecron
Jun 20, 2018·Molecular Carcinogenesis·Guo-Jin WuTian-Rui Xu
Mar 23, 2017·Molecular Neurodegeneration·Alfredo Ramos-MiguelM Julia García-Fuster
Jun 3, 2018·International Journal of Molecular Sciences·Navneet Kumar DubeyWin-Ping Deng
Jun 16, 2012·Molecular Biology Reports·Richa TewariEllora Sen
Sep 13, 2019·European Journal of Medicinal Chemistry·Susana Santos Braga
Aug 31, 2021·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Jincan ChenLanmei Chen

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