Liquid Chromatography Mass Spectrometry (LCMS) and Phenotype Microarray Profiling of Ovarian Cancer Cells After Exposure to Cisplatin

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

“…There was a very clear effect of the combination treatment on the purine and pyrimidine pathways. This was very different from the metabolic shifts observed for melittin and cisplatin alone [ 15 , 24 ], suggesting the combination has quite a different effect on cell metabolism. There was a very large increase in the levels of the adenine metabolite, hypoxanthine, and guanine in both cell lines.…”

“…Significant changes in the levels of various classes of metabolites, especially those in the mitochondrial TCA cycle, energy metabolism, and nucleotide and amino acids metabolism were observed as summarised in Table 1 . The major impression is that the combination of melittin and cisplatin produces distinct metabolic profiles in both cell lines that are unlike those produced when either of the agents are used alone as previously reported [ 15 , 24 ].…”

“…Recent studies have reported that components of bee venom may exert an anti-tumour effect on human ovarian cancer and that the venom has the potential for enhancing the cytotoxic effect of the antitumor agent cisplatin [ 14 ]. Different melittin + cisplatin mechanisms could interact to either reduce or increase anticancer efficacy, thus producing three possible effects: (1) Additive, when the combined effect is equal to the sum of individual effects; (2) Antagonistic, when the effect of one or both compounds is less than when they are applied together than when individually applied; (3) synergism, when the effect of combined substances is greater than the sum of the individual effects [ 24 ]. Our findings show that these effects can occur depending on the concentrations of melittin and cisplatin in the combination.…”

“…There was a very large increase in the levels of the adenine metabolite, hypoxanthine, and guanine in both cell lines. This possibly indicates that the combination of melittin with cisplatin is promoting greater adduct formation between cisplatin and DNA in comparison with the treatment with cisplatin alone, where there was no strong evidence for effects on the levels of DNA bases [ 24 ]. Adducts formed with cisplatin are mainly intra-strand crosslinks joining two guanine residues and to a lesser extent intra-strand links between guanine and adenine [ 32 ].…”

Chick chorioallantoic membrane (CAM) assay for the evaluation of the antitumor and antimetastatic activity of platinum-based drugs in association with the impact on the amino acid metabolism

“…Specifically, an increase of the amino acids upon CDDP treatment was observed, whereas PtNPs showed decrease of the amino acids in significant proportions. These contrasting results imply a higher sensitivity of MDA-MB-231 ​cells towards PtNPs compared to CDDP, since an increase of the amino acids has been related to a degree of insensitivity to various chemotherapeutic agents [ [57] , [58] , [59] ], even when combinatorial effects of melittin or biguanide drugs with CDDP have been introduced [ [60] , [61] , [62] , [63] ].…”