Metabolomic profiling of the effects of melittin on cisplatin resistant and cisplatin sensitive ovarian cancer cells using mass spectrometry and biolog microarray technology

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

3 Citations (Scopus)

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.
LanguageEnglish
Number of pages18
JournalMetabolites
Volume6
Issue number4
DOIs
Publication statusPublished - 13 Oct 2016

Fingerprint

Melitten
Metabolomics
Microarrays
Ovarian Neoplasms
Cisplatin
Mass spectrometry
Mass Spectrometry
Cells
Technology
Cell Line
Lipids
NAD
Bee Venoms
Oncology
Carnitine
Liquid chromatography
Polyamines
Metabolites
Glutamine
Chemical analysis

Keywords

  • metabolomics
  • melittin
  • ovarian cancer
  • LC-MS
  • A2780 cells
  • cisplatin resistance

Cite this

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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 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.",
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author = "Sanad Alonezi and Jonans Tusiimire and Jennifer Wallace and Dufton, {Mark J.} and Parkinson, {John A.} and Young, {Louise C.} and Clements, {Carol J.} and Park, {Jin Kyu} and Jeon, {Jong Woon} and Ferro, {Valerie A.} and Watson, {David G.}",
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Metabolomic profiling of the effects of melittin on cisplatin resistant and cisplatin sensitive ovarian cancer cells using mass spectrometry and biolog microarray technology. / 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. 6, No. 4, 13.10.2016.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Metabolomic profiling of the effects of melittin on cisplatin resistant and cisplatin sensitive ovarian cancer cells using mass spectrometry and biolog microarray technology

AU - Alonezi , Sanad

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

AU - Jeon, Jong Woon

AU - Ferro, Valerie A.

AU - Watson, David G.

PY - 2016/10/13

Y1 - 2016/10/13

N2 - 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.

AB - 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.

KW - metabolomics

KW - melittin

KW - ovarian cancer

KW - LC-MS

KW - A2780 cells

KW - cisplatin resistance

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U2 - 10.3390/metabo6040035

DO - 10.3390/metabo6040035

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JO - Metabolites

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SN - 2218-1989

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