Evaluation of the combined treatment with cisplatin and melatonin on neuroblastoma cell viability and antioxidant capacity

Year 2014, Volume: 31 Issue: 1, 37 - 42, 05.06.2014

Adem Kara , Atakan Yucel Nermin Yucel Halil Ozcan Jale Sellı Deniz Ünal

Abstract

In this study, we investigated the cell viability and antioxidant effects of melatonin both with and without cisplatin (CDDP) on the cultured neuroblastoma cancer cell line. Neuroblastoma
cancer cells were cultured in Dulbecco’s Modified Eagle’s Medium (DMEM) at 37°C with 5% CO2 to examine the cytotoxic effect of melatonin; cells were cultured both CDDP with and without melatonin and thereafter counted in a 48-well microplate. To examine the effect of melatonin and CDDP, cells were divided into ten groups (control, vehicle, melatonin-5nM and10nM, CDDP-50μM and 100μM, melatonin-5nM+CDDP-
50μM, melatonin-5nM+CDDP-100μM, melatonin-10nm+CDDP-50μM and melatonin-10nM+CDDP-100μM) and thereafter cell viability was determined in a 48-well microplate using 3-(4,5-dimetiltriazol-2-il)-2,5- difeniltetrazolium bromid (MTT) assay.
In different series, cells were cultured and treated with ethanol, melatonin, CDDP, and combination of melatonin and CDDP. After harvest, TAS and TOS were measured via
Elisa assay kits. Melatonin and combination of melatonin and CCDP produced no cytotoxic effect on neuroblastoma cancer cells after 24 hours, but a decrease in the cell viability
after 48 hours. Furthermore, CDDP treatment significantly decreased the cell viability both after 24 and 48 hours periods compared to untreated controls. Melatonin enhanced the cytotoxic effects of CDDP after 48 hours neuroblastoma cell lines. Therefore, melatonin may be used as an adjunctive therapy agent to both improve neuroblastoma cancer chemotherapy and depression and for inhibition of CDDP side effects.

J. Exp. Clin. Med., 2014; 31:37-42

Keywords

Antioxidant; cisplatin; cytotoxicity; melatonin; neuroblastoma cell

References

• Alexandre, J., Batteux, F., Nicco, C., Chereau, C., Laurent, A., Guillevin, L., Weill, B., Goldwasser, F., 2006. Accumulation of hydrogen peroxide is an early and crucial step for paclitaxel-induced cancer cell death both in vitro and in vivo. Int. J. Cancer. 119, 41-48. doi: 10.1002/ Ijc.21685.
• American Psychiatric Association. 2000. Diagnostic and statistical manual of mental disorders: DSM-IV-TR. American Psychiatric Publishing Inc, 4 th edition.
• Bairati, I., Meyer, F., Gelinas, M., Fortin, A., Nabid, A., Brochet, F.O., Mercier, J.P., Tetu, B., Harel, F., Abdous, B., Vigneault, P., Vass, S., del Vecchio, P., Roy, J., 2005. Randomized trial of antioxidant vitamins to prevent acute adverse effects of radiation therapy in head and neck cancer patients. J. Clin. Oncol. 23, 5805-5813. doi:10.1200/JCO.2005.05.514.
• Bartsch, C., Bartsch, H., Fuchs, U., Lippert, T. H., Bellmann, O., Gupta, D., 1989. Stage-dependent depression of melatonin in patients with Primary breast-cancer-correlation with prolactin, thyroid stimulating hormone, and steroid-receptors. Cancer. 64, 426-433. doi: 10.1002/1097.
• Blask, D.E., Sauer, L.A., Dauchy, R.T., Holowachuk, E.W., Ruhoff, M.S., Kopff, H.S., 1999. Melatonin inhibition of cancer growth in vivo involves suppression of tumor fatty acid metabolism via melatonin receptor-mediated signal transduction events. Cancer. Res. 59, 4693-4701.
• Brzezinski, A., 1997. Mechanisms of disease: Melatonin in humans. N. Engl. J. Med. 336, 186-195.
• Choi, C.H., Lee, Y.Y., Song, T.J., Park, H.S., Kim, M.K., Kim, T.J., Lee, J.W., Lee, J.H., Bae, D.S., Kim, B.G., 2011. Phase II study of belotecan, a camptothecin analogue, in combination with carboplatin for the treatment of recurrent ovarian cancer. Cancer. 117, 2104-2111. doi: 1002/cncr.25710.
• Colleoni, M., Mandala, M., Peruzzotti, G., Robertson, C., Bredart, A., Goldhirsch, A., 2000. Depression and degree of acceptance of adjuvant cytotoxic drugs. Lancet. 356, 1326-1327.
• Courtet, P., 2012. Circadian dimension and severity of depression. Eur. Psychiat. 27, 476-481.
• Dubocovich, M.L., Delagrange, P., Krause, D.N., Sugden, D., Cardinali, D.P., Olcese, J., 2010. International union of basic and clinical pharmacology. LXXV. Nomenclature, classification, and pharmacology of G protein-coupled melatonin receptors. Pharmacol. Rev. 62, 343-380. doi: 1124/pr.110.002832.
• Erel, O., 2004. A novel automated method to measure total antioxidant response against potent free radical reactions. Clin. Biochem. 37, 112-119.
• Erel, O., 2005. A new automated colorimetric method for measuring total oxidant status. Clinical Biochemistry. 38, 1103-1111.
• Evans, A.E., Dangio, G.J., Randolph, J., 1971. Proposed staging for children with neuroblastoma-childrens cancer study group-A. Cancer. 27, 374-3 doi: 10.1002/1097.
• Futagami, M., Sato, S., Sakamoto, T., Yokoyama, Y., Saito, Y., 2001. Effects of melatonin on the proliferation and cis-diamminedichloroplatinum (CDDP) sensitivity of cultured human ovarian cancer cells. Gynecol. Oncol. 82, 544-549.
• Garcia-Navarro, A., Gonzalez-Puga, C., Escames, G., Lopez, L.C., Lopez, A., Lopez-Cantarero, M., Camacho, E., Espinosa, A., Gallo, M.A., Acuna-Castroviejo, D., 2007. Cellular mechanisms involved in the melatonin inhibition of HT-29 human colon cancer cell proliferation in culture. J. Pineal Res. 43, 195-205.
• Hara, M., Yoshida, M., Nishijima, H., Yokosuka, M., Iigo, M., Ohtani-Kaneko, R., Shimada, A., Hasegawa, T., Akama, Y., Hirata, K., 2001. Melatonin, a pineal secretory product with antioxidant properties, protects against cisplatin-induced nephrotoxicity in rats. J. Pineal Res. 30, 129-1
• Hermann, R., Podhajsky, S., Jungnickel, S., Lerchl, A., 2002. Potentiation of antiproliferative effects of tamoxifen and ethanol on mouse hepatoma cells by melatonin: Possible involvement of mitogen-activated protein kinase and induction of apoptosis. J. Pineal Res. 33, 8-13.
• Hill, S. M., Frasch, T., Xiang, S. L., Yuan, L., Duplessis, T., Mao, L.L., 2009. Molecular mechanisms of melatonin anticancer effects. Integr Cancer Ther. 8, 337-346.
• Hrushesky, W.J.M., 1985. Circadian timing of cancer-chemotherapy. Science. 228, 73-75.
• Karadeniz, A., Simsek, N., Karakus, E., Yildirim, S., Kara, A., Can, I., Kisa, F., Emre, H. Turkeli, M., 2011. Royal jelly modulates oxidative stress and apoptosis in liver and kidneys of rats treated with cisplatin. Oxid. Med. Cell. Longev. doi: 10.1155/2011/981793.
• Kim, J.H., Jeong, S.J., Kim, B., Yun, S.M., Choi, D.Y. Kim, S.H., 2012. Melatonin synergistically enhances cisplatin-induced apoptosis via the dephosphorylation of ERK/p90 ribosomal S6 kinase/heat shock protein 27 in SK-OV-3 cells. J. Pineal Res. 52, 244-252. doi:10.1111/j.1600079X.2011.00935.x.
• Liou, G.Y., Storz, P., 2010. Reactive oxygen species in cancer. Free Radical Res. 44, 479-496. doi: 10.3109/10715761003667554.
• Lissoni, P., Barni, S., Mandala, M., Ardizzoia, A., Paolorossi, F., Vaghi, M., Longarini, R., Malugani, F. Tancini, G., 1999. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur. J. Cancer. 35, 1688-1692.
• Lissoni, P., Paolorossi, F., Ardizzoia, A., Barni, S., Chilelli, M., Mancuso, M., Tancini, G., Conti, A. Maestroni, G.J.M., 1997. A randomized study of chemotherapy with cisplatin plus etoposide versus chemoendocrine therapy with cisplatin, etoposide and the pineal hormone melatonin as a first-line treatment of advanced non-small cell lung cancer patients in a poor clinical state. J. Pineal Res. 23, 15-19.
• Liu, Y., Chen, L., He, X., Fan, L., Yang, G., Chen, X., Lin, X., Du, L., Li, Z., Ye, H., Mao, Y., Zhao, X., Wei, Y., 2008. Enhancement of therapeutic effectiveness by combining liposomal honokiol with cisplatin in ovarian carcinoma. Int. J. Gynecol. Cancer. 18, 652-659.
• Llobet, D., Eritja, N., Encinas, M., Sorolla, A., Yeramian, A., Schoenenberger, J.A., Llombart-Cussacc, A., Martia, R.M., Matias-Guiu, X., Dolcet, X., 2008. Antioxidants block proteasome inhibitor function in endometrial carcinoma cells. Anti-Cancer Drug. 19, 115-124. doi: 1097/CAD.0b013e3282f24031.
• Parlakpinar, H., Sahna, E., Ozer, M., Ozugurlu, F., Vardi, N., Acet, A., 2002. Physiological and pharmacological concentrations of melatonin protect against cisplatin-induced acute renal injury. J. Pineal Res. 33, 161-166.
• Reiter, R.J., Paredes, S.D., Manchester, L.C. Tan, D.X., 2009. Reducing oxidative/nitrosative stress: A newly-discovered genre for melatonin. Crit. Rev. Biochem. Mol. Biol. 44, 175-200. doi: 10.1080/10409230903044914.
• Reiter, R.J., Tan, D.X., Sainz, R.M., Mayo, J.C. Lopez-Burillo, S., 2002. Melatonin: Reducing the toxicity and increasing the efficacy of drugs.
• In conclusion, treatment with melatonin may be attenuated to the toxic effects of ROS in neoplastic patients with CDDP treatment and can be useful in a combination with chemotherapeutic agents to improve the therapeutic effects.