vitamin-k-semiquinone-radical and Melanoma

Topics: Amino Acids; Animals; Ascorbic Acid; Cell Division; Cricetinae; Dietary Fats; Dietary Proteins; Humans; Melanoma; Mice; Nucleosides; Nutritional Physiological Phenomena; Pyridoxine; Skin Neoplasms; Trace Elements; Vitamin A; Vitamin D; Vitamin K

The effects of six lipophilic vitamins: tretinoin (ATRA), vitamin D(3) (VD(3)), VE, VK(1), VK(3), and VK(5) on cell proliferation and apoptosis in human A375 melanoma cells were investigated. VD(3), VK(3), and VK(5) were found to inhibit cell proliferation significantly at concentration ranges of 10-100 μmol/L (p<0.01), while the other vitamins did not show inhibitory effects at 100 μmol/L. VK(3) and VK(5) showed the strongest effects with IC(50) values of less than 10 μmol/L. Dacarbazine slightly inhibited the proliferation of A375 cells at a concentration range of 25-100 μmol/L, but the effects were not statistically significant. VK(3) and VK(5) increased annexin-V positive apoptotic cells, as well as activating caspase-3, in A375 cells. Our findings showed that VD(3), VK(3,) and VK(5) inhibited the growth of dacarbazine resistant human melanoma cells, while ATRA, VE, and VK(1) had little effect on the cell growth. The effects of VK(3) and VK(5) were observed at concentrations lower than 10 μmol/L, which are suggested to have resulted from apoptosis-induction in the melanoma cells.

Topics: Annexin A5; Antineoplastic Agents; Apoptosis; Caspase 3; Cell Line, Tumor; Cell Proliferation; Cholecalciferol; Dacarbazine; Drug Resistance, Neoplasm; Humans; Hydrophobic and Hydrophilic Interactions; Inhibitory Concentration 50; Melanoma; Tretinoin; Vitamin K; Vitamins

We noted that patients treated with high-dose interleukin (IL)-2 (600,000 IU/kg every 8 h by intravenous bolus) at our institution frequently developed prolongation of their prothrombin time (PT). We therefore performed a prospective study of coagulation function during IL-2 treatment. Since IL-2 treated individuals are known to develop cholestatic liver dysfunction, we hypothesized that the hypoprothrombinemia was due to deficiency of liver-synthesized clotting factors and could be prevented by vitamin K replacement. Alternating patients served as controls or received prophylactic subcutaneous subcutaneous vitamin K. While the nine control patients did not exhibit a significant increase (mean +/- SD) in PT (13.6 +/- 0.6 s pretreatment, 15.0 +/- 2.2 on day 4, and 15.0 +/- 2.5 on day 7, p = 0.77 by repeated measures analysis), three patients developed marked increases in PT (greater than 18 s). Changes in partial thromboplastin time (PTT) over this interval were also not statistically significant. Factor VII levels decreased in all patients from 106 +/- 22 to 59 +/- 16 and 52 +/- 26% on days 4 and 7 (p = 0.0002). Factor VII levels in four patients dropped below the lower limit of normal. Prophylactic treatment of seven patients with vitamin K on days 1-8 of the IL-2 therapy protocol resulted in diminished changes in PT and factor VII compared to control patients (p = 0.02 and 0.003 respectively). No vitamin K-treated patient developed PT or Factor VII levels significantly outside the normal range. Prophylactic vitamin K can prevent hypoprothrombinemia in patients treated with IL-2. This may be of importance in patients with decreased hepatic vitamin K stores, who may be at risk for bleeding complications.

Topics: Blood Coagulation; Humans; Hypoprothrombinemias; Interleukin-2; Kidney Neoplasms; Liver; Melanoma; Neoplasm Metastasis; Parenteral Nutrition; Recombinant Proteins; Vitamin K

The effects of buthionine sulphoximine (BSO) treatment on cellular glutathione (GSH) content and on the cytotoxic action of menadione were investigated in cultured IGRI human melanoma cells. Addition of BSO (10(-8)-0.5 X 10(-3) M) to the cultures resulted in a dose- and time-dependent depletion of cellular GSH. BSO (10(-5) and 10(-6) M) did not influence cell multiplication up to 48 h, as determined by trypan blue staining. Menadione (3 X 10(-5) M) treatment decreased the cellular GSH concentration and also reduced cell number after a 24 h exposure. Its cytotoxicity was increased by BSO (10(-5), 10(-6) M), though the potentiating effect was moderate.

Topics: Antimetabolites; Buthionine Sulfoximine; Cell Line; Cell Survival; Cysteine; Glutathione; Humans; Melanoma; Methionine Sulfoximine; Tumor Cells, Cultured; Vitamin K

Using an adapted assay that requires an enzyme aliquot that forms only 5 pmoles vitamin K, we were able to demonstrate vitamin K1 2,3 epoxide reductase activity in cultured B16 mouse melanoma cells. The enzyme uses dithiothreitol, but not NADH as a reducing cofactor and is sensitive to inhibition by warfarin (2% residual activity at 10 micrograms/ml warfarin). Incubation of B16 cells in culture with 30 micrograms/ml warfarin leads to an 45% residual reductase as compared to normally cultured B16 cells. Combined with the reported presence of vitamin K dependent carboxylase in B16 cells and the cytotoxicity of warfarin towards B16 cells this suggests an active vitamin K cycle in these melanoma cells that may be essential for survival.

Topics: Animals; Cattle; Melanoma; Mice; Microsomes, Liver; Mixed Function Oxygenases; Vitamin K; Vitamin K Epoxide Reductases; Warfarin

Topics: Antineoplastic Agents; Colonic Neoplasms; Energy Transfer; Humans; Melanoma; Naphthols; Neoplasms; Pancreatic Neoplasms; Skin Neoplasms; Vitamin K

Topics: 1-Carboxyglutamic Acid; Animals; Cell Line; Glutamates; Kinetics; Lymphoma; Mammary Neoplasms, Experimental; Mast-Cell Sarcoma; Melanoma; Mice; Mice, Inbred BALB C; Microsomes; Neoplasm Proteins; Neoplasms, Experimental; Vitamin K

Topics: Animals; Cell Division; Cells, Cultured; Choline O-Acetyltransferase; Glioma; Melanoma; Mice; Neoplasms, Experimental; Neuroblastoma; Rats; Tyrosine 3-Monooxygenase; Vitamin K

Topics: Animals; Antineoplastic Agents; Autoradiography; Cyclophosphamide; Drug Therapy, Combination; Histocytochemistry; Injections, Intraperitoneal; Injections, Intravenous; Leukocyte Count; Melanoma; Mice; Neoplasms, Experimental; Olivomycins; Organophosphorus Compounds; Prednisolone; Radiation-Sensitizing Agents; Time Factors; Tritium; Vitamin K

Topics: Adult; Antineoplastic Agents; Arsenicals; Breast Neoplasms; Carcinoma, Bronchogenic; Carcinoma, Squamous Cell; Choriocarcinoma; Colonic Neoplasms; Drug Synergism; Female; Fluorides; Heparin; Humans; Lung Neoplasms; Male; Malonates; Melanoma; Neoplasms; Ovarian Neoplasms; Pharyngeal Neoplasms; Pregnancy; Rectal Neoplasms; Sarcoma; Stomach Neoplasms; Testicular Neoplasms; Thyroid Neoplasms; Time Factors; Vitamin K

Topics: Adenocarcinoma; Autoradiography; Colonic Neoplasms; Dysgerminoma; Female; Gallbladder Neoplasms; Hodgkin Disease; Humans; Injections, Intra-Arterial; Injections, Intravenous; Melanoma; Neoplasm Metastasis; Neoplasms; Ovarian Neoplasms; Radiotherapy Dosage; Skin Neoplasms; Tritium; Vitamin K

Topics: Autoradiography; Female; Humans; Leg; Melanoma; Middle Aged; Neoplasms; Radiation Protection; Radioisotopes; Radiotherapy Dosage; Tritium; Ubiquinone; Vitamin K