Metabolomic profiling of the synergistic effects of melittin in combination with cisplatin on ovarian cancer cells

Sanad Alonezi, Jonans Tusiimire, Jennifer Wallace, Mark J. Dufton, John A. Parkinson, Louise C. Young, Carol J. Clements, Jin-Kyu Park, Jong-Woon Jeon, Valerie A. Ferro, David G. Watson

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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.
LanguageEnglish
Pages1-18
Number of pages18
JournalMetabolites
Volume7
Issue number14
DOIs
Publication statusPublished - 14 Apr 2017

Fingerprint

Melitten
Metabolomics
Ovarian Neoplasms
Cisplatin
Cells
Cell Line
Bee Venoms
Oncology
Citric Acid Cycle
Oxidative Phosphorylation
Liquid chromatography
Discriminant Analysis
Discriminant analysis
Metabolites
Principal Component Analysis
Least-Squares Analysis
Drug Resistance
Proline
Metabolism
Liquid Chromatography

Keywords

  • melittin
  • cisplatin
  • synergy
  • sensitive and resistant ovarian cancer cells
  • metabolomics

Cite this

Alonezi, Sanad ; Tusiimire, Jonans ; Wallace, Jennifer ; Dufton, Mark J. ; Parkinson, John A. ; Young, Louise C. ; Clements, Carol J. ; Park, Jin-Kyu ; Jeon, Jong-Woon ; Ferro, Valerie A. ; Watson, David G. / Metabolomic profiling of the synergistic effects of melittin in combination with cisplatin on ovarian cancer cells. In: Metabolites. 2017 ; Vol. 7, No. 14. pp. 1-18.
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abstract = "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 treatmentinduced 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.",
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Metabolomic profiling of the synergistic effects of melittin in combination with cisplatin on ovarian cancer cells. / Alonezi, Sanad; Tusiimire, Jonans; Wallace, Jennifer; Dufton, Mark J.; Parkinson, John A.; Young, Louise C.; Clements, Carol J.; Park, Jin-Kyu; Jeon, Jong-Woon; Ferro, Valerie A.; Watson, David G.

In: Metabolites, Vol. 7, No. 14, 14.04.2017, p. 1-18.

Research output: Contribution to journalArticle

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T1 - Metabolomic profiling of the synergistic effects of melittin in combination with cisplatin on ovarian cancer cells

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AU - Tusiimire, Jonans

AU - Wallace, Jennifer

AU - Dufton, Mark J.

AU - Parkinson, John A.

AU - Young, Louise C.

AU - Clements, Carol J.

AU - Park, Jin-Kyu

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AU - Watson, David G.

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