Morphine inhibits doxorubicin-induced reactive oxygen species generation and nuclear factor kappa B transcriptional activation in neuroblastoma SH-SY5Y cells

doi:10.1042/BJ20070186

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	Morphine inhibits doxorubicin-induced reactive oxygen species generation and nuclear factor kappa B transcriptional activation in neuroblastoma SH-SY5Y cells
	Lin, Xin ; Li, Qing ; Wang, Yu-Jun; Ju, Ya-Wen ; Chi, Zhi-Qiang; Wang, Min-Wei ; Liu, Jing-Gen
刊名	BIOCHEMICAL JOURNAL
	2007-09-01
卷号	406 页码:215-221
关键词	apoptosis doxorubicin (DOX) morphine nuclear factor kappa B reactive oxygen species SH-SY5Y cell
ISSN号	0264-6021
DOI	10.1042/BJ20070186
文献子类	Article
英文摘要	Morphine is recommended as a first-line opioid analgesic in the pain management of cancer patients. Accumulating evidence shows that morphine has anti-apoptotic activity, but its impact on the therapeutic applications of antineoplastic drugs is not well known. The present study was undertaken to test the hypothesis that morphine might antagonize the pro-apoptotic activity of DOX (doxorubicin), a commonly used antitumour drug for the treatment of neuroblastoma, in cultured SH-SY5Y cells. In the present study we demonstrated that morphine suppressed DOX-induced inhibition of cell proliferation and programmed cell death in a concentration-dependent, and naloxone as well as pertussis toxin-irreversible, manner. Further studies showed that morphine inhibited ROS (reactive oxygen species) generation, and prevented DOX-mediated caspase-3 activation, cytochrome c release and changes of Bax and Bc1-2 protein expression. The antioxidant NAC (N-acetylcysteine) also showed the same effects as morphine on DOX-induced ROS generation, caspase-3 activation and cytochrome c release and changes in Bax (Bc1-2-associated X protein) and Bc1-2 protein expression. Additionally, morphine was found to suppress DOX-induced NF-kappa B (nuclear factor kappa B) transcriptional activation via a reduction Of I kappa B alpha (inhibitor of nuclear factor kappa B) degradation. These present findings support the hypothesis that morphine can inhibit DOX-induced neuroblastoma cell apoptosis by the inhibition of ROS generation and mitochondrial cytochrome c release, as well as by blockade of NF-kappa B transcriptional activation, and suggests that morphine might have an impact on the antitumour efficiency of DOX.
WOS关键词	CYTOCHROME-C RELEASE ; INDUCED APOPTOSIS ; HYDROGEN-PEROXIDE ; TUMOR-GROWTH ; CASPASE-3 ACTIVATION ; OXIDATIVE STRESS ; IN-VITRO ; MECHANISM ; DEATH ; ALPHA
WOS研究方向	Biochemistry & Molecular Biology
语种	英语
出版者	PORTLAND PRESS LTD
WOS记录号	WOS:000249181200004
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/273152]
专题	药理学第二研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Liu, Jing-Gen
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 2.Sheyang Pharmaceut Univ, Dept Pharmacol, New Delhi 110016, India
推荐引用方式 GB/T 7714	Lin, Xin,Li, Qing,Wang, Yu-Jun,et al. Morphine inhibits doxorubicin-induced reactive oxygen species generation and nuclear factor kappa B transcriptional activation in neuroblastoma SH-SY5Y cells[J]. BIOCHEMICAL JOURNAL,2007,406:215-221.
APA	Lin, Xin.,Li, Qing.,Wang, Yu-Jun.,Ju, Ya-Wen.,Chi, Zhi-Qiang.,...&Liu, Jing-Gen.(2007).Morphine inhibits doxorubicin-induced reactive oxygen species generation and nuclear factor kappa B transcriptional activation in neuroblastoma SH-SY5Y cells.BIOCHEMICAL JOURNAL,406,215-221.
MLA	Lin, Xin,et al."Morphine inhibits doxorubicin-induced reactive oxygen species generation and nuclear factor kappa B transcriptional activation in neuroblastoma SH-SY5Y cells".BIOCHEMICAL JOURNAL 406(2007):215-221.