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Morphine inhibits doxorubicin-induced reactive oxygen species generation and nuclear factor kappaB transcriptional activation in neuroblastoma SH-SY5Y cells.
Biochem J. 2007 Sep 01; 406(2):215-21.BJ

Abstract

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 Bcl-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 (Bcl-2-associated X protein) and Bcl-2 protein expression. Additionally, morphine was found to suppress DOX-induced NF-kappaB (nuclear factor kappaB) transcriptional activation via a reduction of IkappaBalpha (inhibitor of nuclear factor kappaB) 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-kappaB transcriptional activation, and suggests that morphine might have an impact on the antitumour efficiency of DOX.

Authors+Show Affiliations

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17542780

Citation

Lin, Xin, et al. "Morphine Inhibits Doxorubicin-induced Reactive Oxygen Species Generation and Nuclear Factor kappaB Transcriptional Activation in Neuroblastoma SH-SY5Y Cells." The Biochemical Journal, vol. 406, no. 2, 2007, pp. 215-21.
Lin X, Li Q, Wang YJ, et al. Morphine inhibits doxorubicin-induced reactive oxygen species generation and nuclear factor kappaB transcriptional activation in neuroblastoma SH-SY5Y cells. Biochem J. 2007;406(2):215-21.
Lin, X., Li, Q., Wang, Y. J., Ju, Y. W., Chi, Z. Q., Wang, M. W., & Liu, J. G. (2007). Morphine inhibits doxorubicin-induced reactive oxygen species generation and nuclear factor kappaB transcriptional activation in neuroblastoma SH-SY5Y cells. The Biochemical Journal, 406(2), 215-21.
Lin X, et al. Morphine Inhibits Doxorubicin-induced Reactive Oxygen Species Generation and Nuclear Factor kappaB Transcriptional Activation in Neuroblastoma SH-SY5Y Cells. Biochem J. 2007 Sep 1;406(2):215-21. PubMed PMID: 17542780.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Morphine inhibits doxorubicin-induced reactive oxygen species generation and nuclear factor kappaB transcriptional activation in neuroblastoma SH-SY5Y cells. AU - Lin,Xin, AU - Li,Qing, AU - Wang,Yu-Jun, AU - Ju,Ya-Wen, AU - Chi,Zhi-Qiang, AU - Wang,Min-Wei, AU - Liu,Jing-Gen, PY - 2007/6/5/pubmed PY - 2007/9/5/medline PY - 2007/6/5/entrez SP - 215 EP - 21 JF - The Biochemical journal JO - Biochem. J. VL - 406 IS - 2 N2 - 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 Bcl-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 (Bcl-2-associated X protein) and Bcl-2 protein expression. Additionally, morphine was found to suppress DOX-induced NF-kappaB (nuclear factor kappaB) transcriptional activation via a reduction of IkappaBalpha (inhibitor of nuclear factor kappaB) 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-kappaB transcriptional activation, and suggests that morphine might have an impact on the antitumour efficiency of DOX. SN - 1470-8728 UR - https://www.unboundmedicine.com/medline/citation/17542780/Morphine_inhibits_doxorubicin_induced_reactive_oxygen_species_generation_and_nuclear_factor_kappaB_transcriptional_activation_in_neuroblastoma_SH_SY5Y_cells_ L2 - https://portlandpress.com/biochemj/article-lookup/doi/10.1042/BJ20070186 DB - PRIME DP - Unbound Medicine ER -