Dataset Information

Metabolomics identifies the intersection of phosphoethanolamine with menaquinone- triggered apoptosis in an in vitro model of leukemia

ABSTRACT: Altered metabolism is increasingly acknowledged as an important aspect of cancer, and thus serves as a potentially fertile area for the identification of therapeutic targets or leads. Our recent work using transcriptional data to predict metabolite levels in cancer cells led to preliminary evidence of the antiproliferative role of menaquinone (vitamin K2) in the Jurkat cell line model of acute lymphoblastic leukemia. However, nothing is known about the direct metabolic impacts of menaquinone in cancer, which could provide insights into its mechanism of action. Here, we used metabolomics to investigate the process by which menaquinone exerts antiproliferative activity on Jurkat cells. We first validated the dose-dependent, semi-selective, pro-apoptotic activity of menaquinone treatment on Jurkat cells relative to non-cancerous lymphoblasts. We then used mass spectrometry-based metabolomics to identify systems-scale changes in metabolic dynamics that are distinct from changes induced in noncancerous cells or by other chemotherapeutics. One of the most significantly affected metabolites was phosphoethanolamine, which exhibited a two-fold increase in menaquinone-treated Jurkat cells compared to vehicle-treated cells at 24 h, growing to a five-fold increase at 72 h. Phosphoethanolamine elevation was observed prior to the induction of apoptosis, and was not observed in menaquinonetreated lymphoblasts or chemotherapeutic-treated Jurkat cells. We also validated the link between menaquinone and phosphoethanolamine in an ovarian cancer cell line, suggesting potentially broad applicability of their relationship. This metabolomics-based work is the first detailed characterization of the metabolic impacts of menaquinone treatment and the first identified link between phosphoethanolamine and menaquinone-induced apoptosis.

INSTRUMENT(S): a LECO Pegasus 4D instrument with an Agilent 7683B autosampler, Agilent 7890A gas chromatograph and time-of-flight mass spectrometer

SUBMITTER: Suganthagunthalam Dhakshinamoorthy

PROVIDER: MTBLS226 | MetaboLights | 2015-10-19

REPOSITORIES: MetaboLights

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Dataset's files

Source:

			Action	DRS
	MTBLS226	Other
	FILES	Other
	a_MTBLS226_Jurkat_mass_spectrometry.txt	Txt
	a_MTBLS226_Lymphoblast_mass_spectrometry.txt	Txt
	a_menaquinone_treated_leukemia_metabolite_profiling_mass_spectrometry.txt	Txt

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Publications

Metabolomics identifies the intersection of phosphoethanolamine with menaquinone-triggered apoptosis in an in vitro model of leukemia.

Dhakshinamoorthy Suganthagunthalam S Dinh Nha-Truc NT Skolnick Jeffrey J Styczynski Mark P MP

Molecular bioSystems 20150901 9

Altered metabolism is increasingly acknowledged as an important aspect of cancer, and thus serves as a potentially fertile area for the identification of therapeutic targets or leads. Our recent work using transcriptional data to predict metabolite levels in cancer cells led to preliminary evidence of the antiproliferative role of menaquinone (vitamin K2) in the Jurkat cell line model of acute lymphoblastic leukemia. However, nothing is known about the direct metabolic impacts of menaquinone in ...[more]

PMID: 26175011

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