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Overcoming resistance to TRAIL-induced apoptosis in solid tumor cells by simultaneously targeting death receptors, c-FLIP and IAPs

HUANG, YING ; YANG, XIANG ; XU, TIANRUI ; KONG, QINGHONG ; ZHANG, YAPING ; SHEN, YUEHAI ; WEI, YUNLIN ; WANG, GUANLIN ; CHANG, KWEN-JEN

International journal of oncology, 2016-07, Vol.49 (1), p.153-163 [Periódico revisado por pares]

Athens: D.A. Spandidos

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Título:
Overcoming resistance to TRAIL-induced apoptosis in solid tumor cells by simultaneously targeting death receptors, c-FLIP and IAPs
Autor: HUANG, YING ; YANG, XIANG ; XU, TIANRUI ; KONG, QINGHONG ; ZHANG, YAPING ; SHEN, YUEHAI ; WEI, YUNLIN ; WANG, GUANLIN ; CHANG, KWEN-JEN
Assuntos: Apoptosis ; Brain cancer ; c-FLIP ; Cancer ; Cancer therapies ; cancer therapy ; Care and treatment ; Chemotherapy ; Cytotoxicity ; drug combination ; Drug resistance ; Gene expression ; Genetic aspects ; Health aspects ; IAPs ; Immunoglobulins ; Innovations ; Kinases ; Proteins ; Rodents ; Studies ; TRAIL ; Transcription factors ; Tumors
É parte de: International journal of oncology, 2016-07, Vol.49 (1), p.153-163
Notas: Contributed equally
Descrição: The discovery of the TRAIL protein and its death receptors DR4/5 changed the horizon of cancer research because TRAIL specifically kills cancer cells. However, the validity of TRAIL-based cancer therapies has yet to be established, as most cancer cells are TRAIL-resistant. In this report, we demonstrate that TRAIL-resistance of many cancer cell lines can be overcome after siRNA- or rocaglamide-mediated downregulation of c-FLIP expression and simultaneous inhibition of IAPs activity using AT406, a pan-antagonist of IAPs. Combined triple actions of the TRAIL, the IAPs inhibitor, AT406, and the c-FLIP expression inhibitor, rocaglamide (ART), markedly improve TRAIL-induced apoptotic effects in most solid cancer cell lines through the activation of an extrinsic apoptosis pathway. Furthermore, this ART combination does not harm normal cells. Among the 18 TRAIL-resistant cancer cell lines used, 15 cell lines become sensitive or highly sensitive to ART, and two out of three glioma cell lines exhibit high resistance to ART treatment due to very low levels of procaspase-8. This study provides a rationale for the development of TRAIL-induced apoptosis-based cancer therapies.
Editor: Athens: D.A. Spandidos
Idioma: Inglês

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Overcoming resistance to TRAIL-induced apoptosis in solid tumor cells by simultaneously targeting death receptors, c-FLIP and IAPs

HUANG, YING ; YANG, XIANG ; XU, TIANRUI ; KONG, QINGHONG ; ZHANG, YAPING ; SHEN, YUEHAI ; WEI, YUNLIN ; WANG, GUANLIN ; CHANG, KWEN-JEN

Athens: D.A. Spandidos

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