Metabolomic Profiling of the Effects of Melittin on Cisplatin Resistant and Cisplatin Sensitive Ovarian Cancer Cells Using Mass Spectrometry and Biolog Microarray Technology

Abstract

In the present study, liquid chromatography-mass spectrometry (LC-MS) was employed to characterise the metabolic profiles of two human ovarian cancer cell lines A2780 (cisplatin-sensitive) and A2780CR (cisplatin-resistant) in response to their exposure to melittin, a cytotoxic peptide from bee venom. In addition, the metabolomics data were supported by application of Biolog microarray technology to examine the utilisation of carbon sources by the two cell lines. Data extraction with MZmine 2.14 and database searching were applied to provide metabolite lists. Principal component analysis (PCA) gave clear separation between the cisplatin-sensitive and resistant strains and their respective controls. The cisplatin-resistant cells were slightly more sensitive to melittin than the sensitive cells with IC50 values of 4.5 and 6.8 μg/mL respectively, although the latter cell line exhibited the greatest metabolic perturbation upon treatment. The changes induced by melittin in the cisplatin-sensitive cells led mostly to reduced levels of amino acids in the proline/glutamine/arginine pathway, as well as to decreased levels of carnitines, polyamines, adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide (NAD+). The effects on energy metabolism were supported by the data from the Biolog assays. The lipid compositions of the two cell lines were quite different with the A2780 cells having higher levels of several ether lipids than the A2780CR cells. Melittin also had some effect on the lipid composition of the cells. Overall, this study suggests that melittin might have some potential as an adjuvant therapy in cancer treatment.

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

“…ATP was found to be more reduced in both cell lines when treated with the combinations compared with the results observed previously with melittin monotherapy [15]. It is known that glycolysis provides ATP and energy in most cell types, but cancer cells extensively use glycolysis to sustain anabolism, which is necessary for tumour growth [50].…”

Effect of Melittin on Metabolomic Profile and Cytokine Production in PMA-Differentiated THP-1 Cells

“…Melittin is a 26-mer peptide with a characteristic sequence that provides the peptide chain with amphiphilic detergent-like properties and a high positive charge. It can self-assemble into tetramers depending on conditions [22,23] and has attracted considerable attention for its potential for selective destruction of cancer cells [24,25].…”

Untargeted LC–MS/MS analysis reveals metabolomics feature of osteosarcoma stem cell response to methotrexate

“…Before the metabolomics analysis, the sample and metabolites were prepared as previously described [34]. After isolation of OSCs, parental OS cells and their SCs were enriched in monolayers and when reached 10 6 /ml, cells were treated with MTX, which was adjusted to achieve a final drug concentration, corresponding to the IC50 value as previously determined.…”