title: 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 IC50values 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.
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UK. alonezi-sanad-mohammed-z@strath.ac.uk.
authors.forename: Sanad
authors.initials: S
authors.lastname: Alonezi
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UK. jonans.tusiimire@strath.ac.uk.
authors.forename: Jonans
authors.initials: J
authors.lastname: Tusiimire
authors.affiliation: WestCHEM, Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, UK. jennifer.wallace.101@strath.ac.uk.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Wallace
authors.affiliation: WestCHEM, Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, UK. mark.dufton@strath.ac.uk.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Dufton
authors.affiliation: WestCHEM, Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, UK. john.parkinson@strath.ac.uk.
authors.forename: John A
authors.initials: JA
authors.lastname: Parkinson
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UK. louise.c.young@strath.ac.uk.
authors.forename: Louise C
authors.initials: LC
authors.lastname: Young
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UK. c.j.clements@strath.ac.uk.
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Clements
authors.affiliation: Beesen Co. Ltd., Bio Venture Town, Yuseong Daero 1662, Dae Jeon 34054, Korea. jkypark@live.co.kr.
authors.forename: Jin Kyu
authors.initials: JK
authors.lastname: Park
authors.affiliation: Beesen Co. Ltd., Bio Venture Town, Yuseong Daero 1662, Dae Jeon 34054, Korea. confessor@hanmail.net.
authors.forename: Jong Woon
authors.initials: JW
authors.lastname: Jeon
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UK. v.a.ferro@strath.ac.uk.
authors.forename: Valerie A
authors.initials: VA
authors.lastname: Ferro
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UK. d.g.watson@strath.ac.uk.
authors.forename: David G
authors.initials: DG
authors.lastname: Watson
keywords: A2780 cells; LC-MS; Melittin; cisplatin resistance; metabolomics; ovarian cancer