Disease relevance of Vitamin K3

• That vitamin K1 enhances the benzo(a)pyrene effect while warfarin and vitamin K deficiency inhibit benzo(a)pyrene tumorigenesis indicates that vitamin K1, vitamin K deprivation, or possibly blockade of its metabolic cycle also modulates benzo(a)pyrene metabolism in vivo but by a mechanism or at a site different from the vitamin K3 effect [1].
• We investigated the mechanism of antitumor activity of the water-soluble derivative of menadione, menadione sodium bisulfite (vitamin K3), versus murine leukemia L1210 [2].
• The mean obstruction times were prolonged at a high intake of menaquinone-4 (250 mg/kg body weight/day), and shortened after a similarly high phylloquinone regimen [3].
• Vitamin K3 inhibits growth of human hepatoma HepG2 cells by decreasing activities of both p34cdc2 kinase and phosphatase [4].
• Microscopic aspects of autoschizic cell death in human ovarian carcinoma (2774) cells following vitamin C, vitamin K3 or vitamin C:K3 treatment [5].

High impact information on Vitamin K3

• We investigated whether, using the defined conditions of growing HCC cell lines in tissue culture, addition of the naturally occurring vitamins K1 or K2 or the synthetic vitamin K3 could influence the secretion of immature prothrombin [6].
• The differential therapeutic effects of vitamin K3 at rest and during exercise recovery are probably due to the differential kinetics of each metabolic state [7].
• Vitamin K3 modulation of EGF-receptor interaction is a temperature- and time-dependent phenomenon [8].
• Vitamin K3-induced cell cycle arrest and apoptotic cell death are accompanied by altered expression of c-fos and c-myc in nasopharyngeal carcinoma cells [9].
• We have found that vitamin K3 induces cell cycle arrest and apoptotic cell death in nasopharyngeal carcinoma (NPC) cells, as evaluated by flow cytometry and DNA gel electrophoresis [9].

Chemical compound and disease context of Vitamin K3

• Renal toxicosis attributable to vitamin K3 (menadione sodium bisulfite) was suspected in 5 young adult horses in which acute renal failure developed following parenteral administration of vitamin K3 at the manufacturers' recommended dosages [10].
• Rats given BHT (3000 mg/kg body weight) for up to 21 days, in a diet containing a minimum of 3 ppm vitamin K3 (six times the recommended requirement), showed decreased vitamin K-dependent blood clotting factor activities, demonstrated by increases in factor-specific clotting time assays [11].
• We concluded that vitamin K3 is more effective than vitamin K2 for inhibition of cancer cell growth, and might have an alternative value as an anticancer drug against glioblastoma multiforme [12].
• Circulating levels of vitamin K1, menaquinone-4, and menaquinone-7 in healthy elderly Japanese women and patients with vertebral fractures and patients with hip fractures [13].
• Antiproliferative effects of mitoxantrone in ADR-sensitive and ADR-resistant P388 leukemia cells enhanced by vitamin K3 [14].

Biological context of Vitamin K3

• Vitamin K3 (menadione)-induced oncosis associated with keratin 8 phosphorylation and histone H3 arylation [15].
• We report here the development of a precise and sensitive method for the determination of vitamin K homologues including phylloquinone (PK), menaquinone-4 (MK-4), and menaquinone-7 (MK-7) in human plasma using HPLC-tandem mass-mass spectrometry with atmospheric pressure chemical ionization (LC-APCI-MS/MS) [16].
• The relative effects of phylloquinone and menaquinone-4 on the blood coagulation factor synthesis in vitamin K-deficient rats [17].
• Each of these activities was inhibited by vitamin K3 and similar IC50 values obtained (4.67 +/- 1.46 microM, 2.0 +/- 0.1 microM and 4.7 +/- 0.1 microM respectively) [18].
• Our early reports have indicated that vitamin K3 (VK3) exerts antitumour activity by inhibiting Cdk1 activity and overexpressing the c-myc gene to induce an apoptotic cell death [19].

Anatomical context of Vitamin K3

• The effects of vitamin K3, quinones, fat-soluble vitamins, and various naturally occurring and synthetic compounds on the binding of 125I-epidermal growth factor (EGF) to mink lung cells or murine 3T3 cells in culture were studied [8].
• To show that UVA1 mediates singlet-oxygen damage to the mitochondrial membranes, X-rays, UVB (290-320 nm), 8-methoxypsoralen and UVA, vitamin K3, anti-Fas antibody, and blocking antibody were the negative controls, while rose bengal or protoporphyrin IX with visible light were the positive controls [20].
• In the present study, we investigated whether menaquinone-4 (MK-4) was metabolized in human osteoblasts to act as a cofactor of gamma-glutamyl carboxylase [21].
• The blood-brain barrier models were incubated with menadione (vitamin K3, an intracellular O2- producing agent), and segmental changes in the electrical resistance across the monolayer were compared between the transgenic and the non-transgenic mice [22].
• In NIH 3T3 fibroblasts, vitamin K3 (50-100 microM) alone had no effect on PLD-catalyzed formation of phosphatidylethanol, a marker of PLD activity, but it slightly (10-21%) inhibited the stimulatory effect of phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C (PKC) [23].

Associations of Vitamin K3 with other chemical compounds

• In each case the label was incorporated into menaquinone-4.[2-14C]Mevalonate was incorporated into menaquinone-4 in the crab (Carcinus maenas) only in the presence of menadione, the organism presumably being unable to synthesize the naphthaquinone nucleus [24].
• MATERIALS AND METHODS: The antiproliferative and apoptotic effects of vitamin C alone, vitamin K3 alone, vitamins C plus K3, gemcitabine alone and gemcitabine plus vitamins C plus K3 were assessed in vitro by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, propidium iodide staining and flow cytometry [25].
• Vitamin K2 (1 mg/kg) stimulated clotting factor synthesis for 2 hr, while cis-vitamin K1, vitamin K3, vitamin K1 2,3-epoxide and oral administration of vitamin K1 were ineffective [26].
• A transplasma membrane redox system in Phycomyces blakesleeanus: properties of a ferricyanide reductase activity regulated by iron level and vitamin K3 [27].
• Menadione bisulfite, a watersoluble analog of Vitamin K3 which is a substrate for carbonyl reductase but not aldose reductase, was a competitive inhibitor of chicken aldose reductase with respect to substrate [28].

Gene context of Vitamin K3

• H32, a Non-Quinone Sulfone Analog of Vitamin K3, Inhibits Human Hepatoma Cell Growth by Inhibiting Cdc25 and Activating ERK [29].
• Induction of cytochrome P450 1A1 gene expression by a vitamin K3 analog in mouse hepatoma Hepa-1c1c7 cells [30].
• Nine vitamin K3 analogs were compared with respect to the induction of the cytochrome P450 1A1 (CYP1A1) expression in mouse hepatoma Hepa-1c1c7 cells [30].
• The phosphorylation of growth factor receptor by VK3 was indicated to be functional, since these were connected with growth factor receptor-bound protein 2 (Grb2) and SOS1 [31].
• Menadione (vitamin K3) enhances the mitogenic signal of epidermal growth factor via extracellular signal-regulated kinases [32].

Analytical, diagnostic and therapeutic context of Vitamin K3

• When tumors were induced in ICR/Ha female mice by the intraperitoneal injection of benzo(a)pyrene, those mice given vitamin K3 before or both before and after benzo(a)pyrene had a slower rate of tumor appearance and tumor death rate as compared with those receiving benzo(a)pyrene alone [1].
• Transfusion of 120 ml of frozen fresh plasma led to an immediate increase in the procoagulant activities of vitamin K dependent protein, similar to that found after perfusion of plasma plus vitamin K3 [33].
• A high-performance liquid chromatographic (HPLC) method for the determination of menadione sodium bisulphite (vitamin K3) in animal feed and premixes is described [34].
• High-performance liquid chromatography of menaquinone-4, 2,3-epoxymenaquinone-4, demethylmenaquinone-4 and related compounds [35].
• These factors and their possible effects on the potentiation of ADR cytotoxicity and the therapeutic significance of utilizing vitamin K3 as an adjuvant in the chemotherapy of MDR tumors is discussed [36].

References