vitamin-k-semiquinone-radical and Carcinoma--Squamous-Cell

Nasopharyngeal carcinoma (NPC) is a prevalent cancer in Taiwan. To improve the treatment of NPC, we have extensively searched for effective combination chemotherapies. Our previous studies indicated that vitamin K3 (VK3) inhibits the growth of NPC CG1 cells in vitro. In this study, we further studied the binary/ternary combined effects of VK3 with other anticancer drugs against NPC cells. The antitumor effects of different VK3 combinations against CG1 cells were determined by using MTT assay, and the combined effects were evaluated by a taibologram, a modified isobolographic method being developed in our laboratory for the analyses of binary/ternary combinations of anticancer agents. Binary combinations of VK3 with doxorubicin (DOX), vinblastine (VBL), or 5-fluorouracil (5-FU) result in synergistic effects. For three-drug combinations, a remarkable synergy was found in the combination of VK3, VBL, and 5-FU. These in vitro results will provide useful information not only for further mechanistic studies and but also for future clinical trials of VK3-based cancer chemotherapy of NPC.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cell Survival; Doxorubicin; Drug Screening Assays, Antitumor; Drug Synergism; Drug Therapy, Combination; Fluorouracil; Humans; Male; Middle Aged; Nasopharyngeal Neoplasms; Tumor Cells, Cultured; Vinblastine; Vitamin K

The effects of the antioxidant N-acetyl-cysteine (NAC) were assessed after short term exposure of A431 epithelial cells. The drug was able to protect, at least partially, the cells from the oxidative stress induced by the quinone menadione. In particular, the oxidizing agent-induced cell rounding and detachment from the substrate were strongly impaired by pre-exposure to the compound. The mechanism of such an effect seems to be ascribable to a target effect of the drug on the adhesion properties of the cells. In fact, a modification of morphological features of NAC-exposed cells and of their ability to adhere to different coated substrates was found. These changes resulted in a significant improvement of the A431 tumor cell adhesion pattern which was associated with a noticeable rearrangement of some cytoskeletal components, mainly of the microfilament system. These data add new importance to the subcellular activity of NAC and seem to indicate that the redox status of the cells, i.e. the intracellular balance between proxidants and antioxidants, could also play a role in their adhesive properties.

Topics: Acetylcysteine; Antimetabolites; Buthionine Sulfoximine; Carcinoma, Squamous Cell; Cell Adhesion; Epithelium; Glutamate-Cysteine Ligase; Humans; Methionine Sulfoximine; Microscopy, Electron, Scanning; Microscopy, Fluorescence; Oxidative Stress; Tumor Cells, Cultured; Vitamin K

The cytotoxicities of mitomycin C (MMC) and doxorubicin (DOX) have been proposed to depend on intracellular reduction by reduced flavoproteins. We investigated whether MMC- and DOX-induced cytotoxicity could be inhibited by competing for electrons from reduced flavoproteins by the artificial electron acceptors phenazine methosulfate (PMS), menadione (MEN) and methylene blue (MB). In intact SW-1573 human lung tumor cells these compounds proved to be excellent electron acceptors, as judged from their capacity to induce high levels of cyanide-resistant respiration. In addition, PMS, MEN and MB were found to decrease the cytotoxicity of MMC, by 90, 63 and 29%, respectively, at concentrations that were themselves completely nontoxic. In contrast, DOX cytotoxicity was not detectably affected. These results suggest that in SW-1573 cells flavoprotein-mediated bioreduction is required for the cytotoxic effect of MMC, but not for that of DOX.

Topics: Carcinoma, Squamous Cell; Doxorubicin; Drug Interactions; Ellipticines; Humans; Lung Neoplasms; Methylene Blue; Methylphenazonium Methosulfate; Mitomycin; Mitomycins; Oxygen Consumption; Peroxides; Phenazines; tert-Butylhydroperoxide; Tumor Cells, Cultured; Vitamin K

The effects of sodium ascorbate (vitamin C) and 2-methyl-1,4-naphthoquinone (vitamin K3) administered separately or in combination on the in vitro cultured human neoplastic cell lines MCF-7 (breast carcinoma), KB (oral epidermoid carcinoma), and AN3-CA (endometrial adenocarcinoma) have been examined. When given separately, vitamin C or K3 had a growth inhibiting action only at high concentrations (5.10(3) mumol/1 and 10(5) nmol/l, respectively). Combined administration of both vitamins demonstrated a synergistic inhibition of cell growth at 10 to 50 times lower concentrations. At this level separately given vitamins are not toxic. The sensitivity to this treatment was somewhat different in the three cell lines, being slightly higher for KB line. This tumor cell growth inhibitory effect was completely suppressed by the addition of catalase to the culture medium containing vitamins C and K3, suggesting an excessive production of hydrogen peroxide as being implied in mechanisms responsible for the above-mentioned effects.

Topics: Adenocarcinoma; Ascorbic Acid; Breast Neoplasms; Carcinoma, Squamous Cell; Catalase; Cell Division; Drug Synergism; Female; Humans; Mouth Neoplasms; Tumor Cells, Cultured; Uterine Neoplasms; 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; Adult; Animals; Arsenicals; Carcinoma, Ehrlich Tumor; Carcinoma, Squamous Cell; Choriocarcinoma; DNA, Neoplasm; Female; Fluorides; Heparin; Humans; Lung Neoplasms; Lymphoma; Male; Malonates; Mandibular Neoplasms; Mice; Middle Aged; Neoplasms; Pregnancy; RNA, Neoplasm; Sarcoma; Testicular Neoplasms; Vitamin K

Topics: Carcinoma, Squamous Cell; Humans; Oxidoreductases; Skin Neoplasms; Succinate Dehydrogenase; Vitamin K

Topics: Carcinoma; Carcinoma, Squamous Cell; Cheek; Cobalt Isotopes; Humans; Injections, Intravenous; Mouth Neoplasms; Neoplasms; Tongue Neoplasms; Vitamin K