menaquinone-6 and phosphorylethanolamine

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 non-cancerous 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 menaquinone-treated 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.

Topics: Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cell Proliferation; Ethanolamines; Humans; Jurkat Cells; Leukemia; Metabolome; Metabolomics; Vitamin K 2

A facultatively anaerobic, non-pigmented, non-spore-forming bacterium was isolated from a littoral wetland of a boreal lake located on Valaam Island, northern Russia, and designated strain P105(T). Cells of this isolate were Gram-negative, non-motile rods coated by S-layers with p2 lattice symmetry. Sugars were the preferred growth substrates. Under anoxic conditions, strain P105(T) was capable of fermentation and dissimilatory Fe(III) reduction. End products of fermentation were acetate, propionate and H2. Strain P105(T) was a mildly acidophilic, mesophilic organism, capable of growth at pH 4.0-7.2 (optimum pH 5.5-6.0) and at 4-35 °C (optimum at 20-28 °C). The major fatty acids were iso-C(15 : 0) and C(16 : 1)ω7c; the cells also contained significant amounts of 13,16-dimethyl octacosanedioic acid (isodiabolic acid). The major polar lipids were phosphocholine and phosphoethanolamine; the quinone was MK-8. The G+C content of the DNA was 60.5 mol%. 16S rRNA gene sequence analysis showed that strain P105(T) belongs to subdivision 3 of the Acidobacteria and is only distantly related (90% sequence similarity) to the only currently characterized member of this subdivision, Bryobacter aggregatus. The novel isolate differs from Bryobacter aggregatus in its cell morphology and ability to grow under anoxic conditions and in the presence of iron- and nitrate-reducing capabilities as well as quinone and polar lipid compositions. These differences suggest that strain P105(T) represents a novel genus and species, for which the name Paludibaculum fermentans gen. nov., sp. nov., is proposed. The type strain of Paludibaculum fermentans is P105(T) ( = DSM 26340(T) = VKM B-2878(T)).

Topics: Acidobacteria; Bacterial Typing Techniques; Base Composition; DNA, Bacterial; Ethanolamines; Fatty Acids; Iron; Lakes; Molecular Sequence Data; Phosphorylcholine; Phylogeny; RNA, Ribosomal, 16S; Russia; Sequence Analysis, DNA; Vitamin K 2; Wetlands