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Metabolites 2017, 7(2), 14; doi:10.3390/metabo7020014

Metabolomic Profiling of the Synergistic Effects of Melittin in Combination with Cisplatin on Ovarian Cancer Cells

Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UK
Department of Pharmacy, Faculty of Medicine, Mbarara University of Science and Technology, P.O. Box 1410 Mbarara, Uganda
WestCHEM Department of Pure and Applied Chemistry, University of Strathclyde, Glasgow G1 1XL, UK
#204, Beesen Co. Ltd., Bio Venture Town, Yuseong Daero 1662, Dae Jeon 34054, Korea
Author to whom correspondence should be addressed.
Academic Editor: Peter Meikle
Received: 17 March 2017 / Revised: 10 April 2017 / Accepted: 12 April 2017 / Published: 14 April 2017
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Melittin, the main peptide present in bee venom, has been proposed as having potential for anticancer therapy; the addition of melittin to cisplatin, a first line treatment for ovarian cancer, may increase the therapeutic response in cancer treatment via synergy, resulting in improved tolerability, reduced relapse, and decreased drug resistance. Thus, this study was designed to compare the metabolomic effects of melittin in combination with cisplatin in cisplatin-sensitive (A2780) and resistant (A2780CR) ovarian cancer cells. Liquid chromatography (LC) coupled with mass spectrometry (MS) was applied to identify metabolic changes in A2780 (combination treatment 5 μg/mL melittin + 2 μg/mL cisplatin) and A2780CR (combination treatment 2 μg/mL melittin + 10 μg/mL cisplatin) cells. Principal components analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) multivariate data analysis models were produced using SIMCA-P software. All models displayed good separation between experimental groups and high-quality goodness of fit (R2) and goodness of prediction (Q2), respectively. The combination treatment induced significant changes in both cell lines involving reduction in the levels of metabolites in the tricarboxylic acid (TCA) cycle, oxidative phosphorylation, purine and pyrimidine metabolism, and the arginine/proline pathway. The combination of melittin with cisplatin that targets these pathways had a synergistic effect. The melittin-cisplatin combination had a stronger effect on the A2780 cell line in comparison with the A2780CR cell line. The metabolic effects of melittin and cisplatin in combination were very different from those of each agent alone. View Full-Text
Keywords: melittin; cisplatin; synergy; sensitive and resistant ovarian cancer cells; metabolomics melittin; cisplatin; synergy; sensitive and resistant ovarian cancer cells; metabolomics

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MDPI and ACS Style

Alonezi, S.; Tusiimire, J.; Wallace, J.; Dufton, M.J.; Parkinson, J.A.; Young, L.C.; Clements, C.J.; Park, J.-K.; Jeon, J.-W.; Ferro, V.A.; Watson, D.G. Metabolomic Profiling of the Synergistic Effects of Melittin in Combination with Cisplatin on Ovarian Cancer Cells. Metabolites 2017, 7, 14.

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