vitamin-k-semiquinone-radical and Ovarian-Neoplasms

The main function of vitamin K in the human organism is its activity in the blood clotting cascade. Epidemiological studies suggest that reduced intake of vitamin K may contribute to an increased risk of geriatric diseases such as atherosclerosis, dementia, osteoporosis, and osteoarthritis. A growing number of studies also indicate that vitamin K may be involved not only in preventing the development of certain cancers but it may also support classical cancer chemotherapy. This review article summarizes the results of studies on the anticancer effects of vitamin K on selected female malignancies, i.e., breast, cervical, and ovarian cancer, published over the past 20 years. The promising effects of vitamin K on cancer cells observed so far indicate its great potential, but also the need for expansion of our knowledge in this area by conducting extensive research, including clinical trials.

Topics: Aged; Blood Coagulation; Female; Humans; Neoplasms; Osteoporosis; Ovarian Neoplasms; Vitamin K; Vitamin K 1; Vitamin K 2

In this study, we examined the effects of vitamin K(2) (menaquinone 4), which has a geranylgeranyl side chain, on various lines of cells derived from human solid tumors and compared them with the effects of geranylgeraniol (GGO).. Cell proliferation was determined with 3'-[1-[(phenylamino)carbonyl]-3,4-tetrazolium- bis (4-methoxy-6-nitro) benzene-sulfonic acid hydrate (XTT), and the induction of apoptosis was analyzed by TUNEL staining and flow cytometry as well as by measurement of DNA fragmentation, released nucleosomes and caspase-3 activity. Levels of Bcl-2, Bax and cytochrome c were determined by immunoblotting.. GGO inhibited the growth of all eight cell lines derived from solid tumors, while vitamin K(2) selectively inhibited the proliferation of ovarian TYK-nu and pancreatic MIA PaCa-2 cancer cells, inducing apoptosis in both cell lines. Far more time was required for the induction of apoptosis in these two cell lines by vitamin K(2) than by GGO. Apoptotic signals induced in TYK-nu cells during the first 2 days that followed the addition of vitamin K(2) to the culture medium were reversible, but these signals became irreversible after 3 days of treatment with vitamin K(2). The induction of apoptosis in TYK-nu cells by vitamin K(2) was inhibited by cycloheximide and also by starvation at a low concentration of serum. Neither cycloheximide nor starvation had any effect on the induction of apoptosis by GGO. Cytochrome c was released simultaneously with the initiation of apoptosis on treatment of TYK-nu cells with vitamin K(2) or GGO. However, GGO induced the release of cytochrome c from isolated mitochondria, while vitamin K(2) did not. The amount of Bcl-2 in TYK-nu cells was reduced by vitamin K(2), but not by GGO.. In contrast to GGO, vitamin K(2) induced apoptosis selectively in pancreatic MIA-PaCa 2 and ovarian TYK-nu cancer cells. It is suggested that de novo protein synthesis might be necessary for induction of apoptosis by vitamin K(2) but not by GGO, and thus, that vitamin K(2) and GGO might induce apoptosis by different mechanisms.

Topics: Apoptosis; bcl-2-Associated X Protein; Caspase 3; Caspases; Cell Division; Cell Separation; Cytochrome c Group; Diterpenes; DNA Fragmentation; Female; Flow Cytometry; Humans; In Situ Nick-End Labeling; Male; Mitochondria; Ovarian Neoplasms; Pancreatic Neoplasms; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; Tumor Cells, Cultured; Vitamin K

We report the case of a patient who was admitted in hospital for evaluation of a superior vena cava thrombosis. The patient exhibited an activated protein C resistance due to an arginine-506 mutation in factor V. Thoracic CT-scan showed a non-compressive complete superior vena cava thrombosis. Other investigations revealed a pleural effusion associated with an ovarian tumor. Pathological data of pleural biopsies showed a papillar carcinoma. Ovarian neoplasia revealed by a paraneoplasic syndrome was diagnosed. Treatment associated cyclophosphamide and carboplatin with anti-K-vitamin was administrated, with a complete remission and disappearance of superior vena cava thrombosis at 27 months of evolution. At this date, we observed a local pelvis recurrence which was treated with paclitaxel associated with surgery.

Topics: Anticoagulants; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Papillary; Cyclophosphamide; Factor V; Female; Humans; Middle Aged; Mutation; Ovarian Neoplasms; Paraneoplastic Syndromes; Pleural Effusion; Protein C; Protein C Deficiency; Remission Induction; Superior Vena Cava Syndrome; Vitamin K

The action of derivatives of polyoxyethylene oxide (triton X-100, triton X-305, tween 21, tween 40, tween 60, and tween 80) on respiration of Ehrlich's tumor and rats ovarium tumor cells involved inhibition of the cells respiration due to alteration of commonly uncorrelated with the distribution of detergents between the cell and the extracellular milieu.

Topics: Animals; Antimycin A; Carcinoma, Ehrlich Tumor; Cytochromes; Dose-Response Relationship, Drug; Female; Glycolysis; In Vitro Techniques; Neoplasms, Experimental; Ovarian Neoplasms; Oxygen Consumption; Polyethylene Glycols; Polysorbates; Quaternary Ammonium Compounds; Rats; Rotenone; Spectrum Analysis; Tetramethylphenylenediamine; Vitamin K

An attempt has been made to develop tritiated derivatives of Synkavit (menadiol sodium diphosphate, MNDP) of high specific activity as a radioactive drug.This paper summarizes the preliminary biological and physical studies, with emphasis on approximate radiation dosimetry and the necessary preliminary testing, and then gives an account of the clinical investigations and the trials carried out so far, which correspond essentially to Phases I and II trials for a chemotherapeutic agent.In all, 214 patients with different sites and types of advanced and recurrent, inoperable, histologically verified malignant tumours including reticuloses have been treated with doses of at least 1 Ci of the various preparations. Among the 203 evaluable treated cases, some form of response was observed in 23 out of 151 (15·2%) receiving the drug by intravenous injections and 13 out of 52 (25%) after intra-arterial injections. For the sites and types of malignant diseases which showed responses after either intravenous or intra-arterial administration among the 55 patients surviving at least 3 months after the first injection, some form of response was observed in 32 but only 5 of these showed either a "complete" or a "partial" response.It is concluded that further investigation is desirable. It is suggested that clinical trials with randomization should be carried out for inoperable cases of carcinoma of the colon and of the pancreas.

Topics: Adult; Aged; Animals; Breast Neoplasms; Carcinoma 256, Walker; Colonic Neoplasms; Culture Techniques; Dose-Response Relationship, Radiation; Female; Half-Life; Hodgkin Disease; Humans; Injections, Intra-Arterial; Injections, Intraperitoneal; Injections, Intravenous; Male; Methods; Middle Aged; Neoplasms; Ovarian Neoplasms; Palatal Neoplasms; Radionuclide Imaging; Rectal Neoplasms; Testicular Neoplasms; Tongue Neoplasms; 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: Dietary Proteins; Estrogens; Female; Humans; Liver; Liver Function Tests; Ovarian Neoplasms; Sicily; Vitamin A; Vitamin K; Vitamins