Ebselen sensitizes glioblastoma cells to Tumor Necrosis Factor (TNFalpha)-induced apoptosis through two distinct pathways involving NF-kappaB downregulation and Fas-mediated formation of death inducing signaling complex

International Journal of Cancer. Journal International Du Cancer
Vivek SharmaEllora Sen

Abstract

Resistance to tumor necrosis factor (TNFalpha)-induced apoptosis in various cancer cells has been attributed to the activation of the transcription factor NF-kappaB. Ebselen (2-phenyl-1,2-benzisoselenazol-3[2H]one)-a selenoorganic compound is known to prevent TNFalpha-mediated NF-kappaB activity. As glioblastoma are resistant to the cytotoxic effect of TNFalpha, we investigated the potential of Ebselen in sensitizing glioma cells to TNFalpha-induced apoptosis. Although treatment with Ebselen reduced viability of glioma cells, cotreatment with TNFalpha enhanced apoptosis further through alteration of TNFalpha-mediated signaling pathways. Sensitization of TNFalpha activated glioma cells to apoptosis by Ebselen involved 2 pathways: (i) abrogation of TNFalpha induced NF-kappaB activation and (ii) induction of Fas-associated death inducing signaling complex (DISC) formation. Ebselen inhibited the prosurvival pathway mediated by NF-kappaB by altering the association of TNF receptor associated factor 2 (TRAF2) with TNFalpha receptor associated death domain (TRADD) in the TNFR1-TRADD-TRAF2 complex -an interaction crucial for mediating NF-kappaB activity. Ebselen also induced the formation of DISC involving Fas, Fas-associated death dom...Continue Reading

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Citations

Sep 3, 2011·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Richa TewariEllora Sen
May 4, 2017·International Journal of Radiation Biology·Noura M Thabet, Enas M Moustafa
Apr 23, 2009·Molecular Oncology·Richa TewariEllora Sen
Nov 20, 2018·Journal of Enzyme Inhibition and Medicinal Chemistry·Albertus Eka Yudistira SarwonoMakoto Ubukata
Dec 27, 2018·International Journal of Molecular Sciences·Heng Wee TanYan-Ming Xu
Jul 9, 2009·Journal of Cellular and Molecular Medicine·Vivek SharmaEllora Sen
Nov 30, 2019·Chemical Communications : Chem Comm·Zhen ChenTianfeng Chen
Jul 4, 2012·Molecular Carcinogenesis·Ruchi GhildiyalEllora Sen
May 29, 2014·Molecular Biology Reports·Gajendra Kumar Azad, Raghuvir S Tomar
Jun 16, 2012·Molecular Biology Reports·Richa TewariEllora Sen
Jul 19, 2017·Journal of Experimental & Clinical Cancer Research : CR·Jin WangPeng Zhao
Aug 18, 2020·Cancer Management and Research·Qi FengShuai Zhang
Jan 28, 2021·International Journal of Molecular Sciences·Dominika RadomskaKrzysztof Bielawski
Jul 4, 2021·European Journal of Medicinal Chemistry·Hongyan ChuaiMinhang Xin
May 14, 2011·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Tingting LinJiacong Shen

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