Ferdowsi University of Mashhad

Document Type : Research Articles

Authors

1 Kharazmi University, Tehran, Iran

2 Tehran University of Medical Science, Tehran, Iran

Abstract

Morphine as an analgesic drug is used frequently in cancer patients. Contradictory results have been achieved from previous studies related to morphine effects in different concentrations. In current study, we examined the effect of clinical concentrations of morphine on A2780Cp cell line related to ovarian cancer. Moreover, its effect on the cytotoxicity of cisplatin was investigated. A2780CP cells were cultured in RPMI1640 medium and treated with clinical doses of morphine alone or in combination with cisplatin. The rate of cell proliferation was measured using MTT assay, morphological changes of nuclei were revealed by 4′,6-diamidino-2-phenylindole (DAPI) staining, and expression of B-cell lymphoma 2 (Bcl-2) was measured using flowcytometry. MTT assay results showed clinical concentration of morphine had no effect on viability of A2780CP cells and toxicity of cisplatin. DAPI staining revealed no chromatin condensation in presence of morphine, and flowcytometry analysis showed that the expression of Bcl-2 in treated cells did not differ from control cells. In accordance with findings in other kinds of cancer, our results demonstrated that morphine did not interact with the function of cispatin in ovarian cancer. This finding can be considered in clinical applications of morphine.

Keywords

Agrez M., Garg M., Dorahy D. and Ackland S. (2011). Synergistic Anti-Tumor Effect of Cisplatin When Combined with an Anti-Src Kinase Integrin-Based Peptide. Journal of cancer therapy 02: 295-301.
Bhat R. S., Bhaskaran M., Mongia A., Hitosugi N. and Singhal P. C. (2004). Morphine-induced macrophage apoptosis: oxidative stress and strategies for modulation. Journal of leukocyte biology 75: 1131-1138.
Bimonte S., Barbieri A., Palma G. and Arra C. (2013). The role of morphine in animal models of human cancer: does morphine promote or inhibit the tumor growth? Biomed research international 2013: 258141.
Bimonte S., Barbieri A., Rea D., Palma G., Luciano A., Cuomo A., Arra C. and Izzo F. (2015). Morphine Promotes Tumor Angiogenesis and Increases Breast Cancer Progression. Biomed research international 2015: 161508.
Cao L. H., Li H. T., Lin W. Q., Tan H. Y., Xie L., Zhong Z. J. and Zhou J. H. (2016). Morphine, a potential antagonist of cisplatin cytotoxicity, inhibits cisplatin-induced apoptosis and suppression of tumor growth in nasopharyngeal carcinoma xenografts. Scientific reports 6: 18706.
Chen Y., Qin Y., Li L., Chen J., Zhang X. and Xie Y. (2017). Morphine Can Inhibit the Growth of Breast Cancer MCF-7 Cells by Arresting the Cell Cycle and Inducing Apoptosis. Biological and pharmaceutical bulletin 40: 1686-1692.
Cheng W. F., Chen L. K., Chen C. A., Chang M. C., Hsiao P. N., Su Y. N., Lee C. N., Jeng H. J., Hsieh C. Y. and Sun W. Z. (2006). Chimeric DNA Vaccine Reverses Morphine-Induced Immunosuppression and Tumorigenesis. Molecular therapy 13: 203-210.
Crawford K. W. and Bowen W.D. (2002). Sigma-2 Receptor Agonists Activate a Novel Apoptotic Pathway and Potentiate Antineoplastic Drugs in Breast Tumor Cell Lines. Cancer research 62:313–322.
Diao C. T. M., Li L., Lau S. Y., Wong T. M. and Wong N. S. (2000). k-Opioid receptor potentiates apoptosis via a phospholipase C pathway in the CNE2 human epithelial tumor cell line. Biochimica et Biophysica Acta 1499:49-62.
Donahue R. N., McLaughlin P. J. and Zagon I. S. (2009). Cell proliferation of human ovarian cancer is regulated by the opioid growth factor-opioid growth factor receptor axis. American journal of physiology regulatory integrative Comparative physiology 296: R1716-R1725.
Gach K., Wyrębska A., Fichna J. and Janecka A. (2011). The role of morphine in regulation of cancer cell growth. Naunyn-Schmiedeberg's Arch Pharmacol 384: 221-230.
Gonzalez V. M., Fuertes M.A., Alonso C. and Perez J. M. (2001). Is cisplatin-induced cell death always produced by apoptosis? Molecular Pharmacology 59: 657-663.
Gupta K., Kshirsagar S., Chang L., Schwartz R., Law P. Y., Yee D. and Hebbel R. P. (2002). Morphine Stimulates Angiogenesis by Activating Proangiogenic and Survivalpromoting Signaling and Promotes Breast Tumor Growth. Cancer Research 62: 4491–4498.
Harimaya Y., Koizumi K., Andoh T., Nojima H., Kuraishi Y. and Saiki I. (2002). Potential ability of morphine to inhibit the adhesion, invasion and metastasis of metastatic colon 26-L5 carcinoma cells. Cancer Letters 187:121–127.
Harper P., Hald O., Lwaleed BA., Kyylay A., Johnston D., Cooper AJ. and Birch B. (2018). The impact of morphine treatment on bladder cancer cell proliferation and apoptosis: in vitro studies. Experimental oncology 40: 190-193.
Hatsukari I., Hitosugi N., Ohno R., Hashimoto K., Nakamura S., Satoh K., Nagasaka H., Matsumoto I. and Sakagami H. (2007). Induction of apoptosis by morphine in human tumor cell lines in vitro. Anticancer Research 27: 857-864.
Hsiao P. N., Chang M. C., Cheng W. F., Chen C. A., Lin H. W., Hsieh C. Y. and Sun W. Z. (2009). Morphine induces apoptosis of human endothelial cells through nitric oxide and reactive oxygen species pathways. Toxicology 256: 83-91.
Iglesias M. (2003). μ-opioid receptor activation prevents apoptosis following serum withdrawal in differentiated SH-SY5Y cells and cortical neurons via phosphatidylinositol 3-kinase. Neuropharmacology 44: 482-492.
Kapasi A. A., Coscia S. A., Pandya M. P. and Singhal P. C. (2004). Morphine modulates HIV-1 gp160-induced murine macrophage and human monocyte apoptosis by disparate ways. ‎Journal of Neuroimmunology 148: 86-96.
Koodie L., Ramakrishnan S. and Roy S. (2010). Morphine Suppresses Tumor Angiogenesis through a HIF-1α/p38MAPK Pathway. American Journal of Pathology 177: 984-997.
Lazarczyk M., Matyja E. and Lipkowski A. W. (2010). A comparative study of morphine stimulation and biphalin inhibition of human glioblastoma T98G cell proliferation in vitro. Peptides 31: 1606-1612.
Maneckjee R., Biswas R. and Vonderhaar B. K. (1990). Binding of opioids to human MCF-7 breast cancer cells and their effects on growth. Cancer Reserch 50: 2234-2238.
Nabiuni M., Jalali H. and Rezaeigazik M. (2015). The effect of morphine on the proliferation of human ovarian epithelial cancer A2780cp cell line. International Journal of Cellular & Molecular Biotechnology 1-9.
Naoko S., Eisaburo S., Sachiko O. and Hirota F. (1996). Anti-cancer effects of morphine through inhibition of tumour necrosis factor-a release and mRNA expression. Carcinogenesis 17: 2337-2341.
Sarah K., Donna H. and Ginger B. (2004). Postmortem Morphine Concentrations Following Use of a Continuous Infusion Pum. Journal of analytical toxicology 28: 529-532.
Tanida S., Mizoshita T., Ozeki K., Tsukamoto H., Kamiya T., Kataoka H., Sakamuro D. and Joh T. (2012). Mechanisms of Cisplatin-Induced Apoptosis and of Cisplatin Sensitivity: Potential of BIN1 to Act as a Potent Predictor of Cisplatin Sensitivity in Gastric Cancer Treatment. International Journal of Surgical Oncology 2012: 862879.
Tegeder I., Gro¨sch S., Schmidtko A., Ha¨ussler A., Schmidt H., Niederberger E., Scholich K. and Geisslinger G. (2003). G Protein-independent G1 Cell Cycle Block and Apoptosis with Morphine in Adenocarcinoma Cells: Involvement of p53 Phosphorylation. Cancer Research 63: 1846–1852.
CAPTCHA Image