ascorbic-acid and Carcinoma-256--Walker

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Carcinoma 256, Walker; Guinea Pigs; Leukemia; Neoplasms; Neoplasms, Experimental; Rats; Research; Sarcoma; Sarcoma, Experimental; Sarcoma, Yoshida

The results of several experimental studies have shown that ascorbic acid inhibits tumor growth and metastasis. Ascorbic acid is an antioxidant that acts as a scavenger for a wide range of reactive oxygen species (ROS). Both tumour metastasis and cell migration have been correlated with the intracellular ROS level, so it was postulated that the inhibitory effect of ascorbic acid derivatives on cell motility may be caused by scavenging of ROS. Time-lapse analyses of Walker 256 carcinosarcoma cell migration showed that both the speed of movement and the cell displacement were inhibited by ascorbic acid applied in concentrations ranging from 10 to 250 microM. This effect correlated with a reduction in the intracellular ROS level in WC 256 cells, suggesting that ROS scavenging may be a mechanism responsible for the inhibition of WC 256 cell migration. However, another potent antioxidant, N-acetyl-L-cysteine, also efficiently decreased the intracellular ROS level in WC 256 cells, but did not affect the migration of the investigated cells. These results demonstrate that intact, unmodified ascorbic acid applied in physiologically relevant and non-toxic concentrations exerts an inhibitory effect on the migration of WC 256 carcinosarcoma cells, and that this may be one of the factors responsible for the anti-metastatic activity of vitamin C. However, our data does not support the hypothesis that the scavenging of intracellular ROS is the main mechanism in the inhibition of cancer cell migration by ascorbic acid.

Topics: Animals; Antioxidants; Ascorbic Acid; Carcinoma 256, Walker; Cell Line, Tumor; Cell Migration Inhibition; Cell Movement; Rats; Reactive Oxygen Species; Sarcoma

CuPu(Py)2 and CuPu(Im)2, two novel dischiffbase coordinated low Mr active centre analogues of Cu2Zn2 superoxide dismutase, were shown to effectively catalyze the production of hydroxyl radicals in the presence and absence of TPA-activated polymorphonuclear leukocytes. These stable copper chelates exhibited a pronounced anticarcinogenic reactivity in male Sprague Dawley rats implanted with Walker 256 carcinosarcoma cells. When four doses of 5 mumol/kg CuPu(Py)2 and CuPu(Im)2, respectively, were administered intratumorally, reduction in tumor size, delay of metastasis and a significant increase in survival of the hosts were observed, resulting in 75% of total remissions. 60% of the animals recovered totally from the carcinosarcoma, when CuPu(Py)2 was applicated intravenously.

Topics: Animals; Antineoplastic Agents; Antioxidants; Ascorbic Acid; Carcinoma 256, Walker; Copper; Free Radicals; Hydrogen Peroxide; Male; Neoplasm Metastasis; Neoplasm Transplantation; Neutrophils; Organometallic Compounds; Oxygen; Rats; Rats, Inbred Strains; Remission Induction; Schiff Bases; Structure-Activity Relationship; Superoxide Dismutase

Topics: Animals; Ascorbic Acid; Binding, Competitive; Carcinoma 256, Walker; Cyclic AMP; Kinetics; Liver; Phosphodiesterase Inhibitors; Protein Binding; Rats

Normal and tumour tissues from rats, blood from normal and tumour bearing rats, and normal human blood were examined using the electron paramagnetic resonance (epr) technique. At low temperature a triplet epr signal, which is known to be produced by a NO-haemoprotein complex, was detected in some tumour samples and in decaying normal liver. At room temperature all of the tumour samples examined gave a doublet signal. This signal was also detected in blood but not in other normal tissues. The signal has a g value of 2·0054 ± 0·0002 and a hyperfine splitting of 1·80 ± 0·05 G and is assigned to the ascorbyl free radical. Model experiments suggest that the appearance of detectable concentrations of this radical result from a disturbance of the normal state of the ascorbic acid, dehydroascorbic acid redox system. It was verified that cell division is not responsible for the ascorbyl radical although autolysis may be involved. A possible relationship between the formation of ascorbyl radicals and other paramagnetic species in tumours is discussed.

Topics: Animals; Ascorbic Acid; Autolysis; Blood Proteins; Carcinoma 256, Walker; Carcinoma, Hepatocellular; Cell Division; Electron Spin Resonance Spectroscopy; Liver Neoplasms; Lung Neoplasms; Methods; Models, Biological; Models, Chemical; Neoplasms; Nitric Oxide; Oxidation-Reduction; Rats; Sarcoma, Yoshida; Temperature

Topics: Animals; Antineoplastic Agents; Ascorbic Acid; Carcinoma 256, Walker; Cell Line; Folic Acid Antagonists; Leukemia L1210; Leukemia, Experimental; Methotrexate; Mice; Mice, Inbred Strains; Oxidation-Reduction; Rats; Rats, Inbred Strains

Topics: Animals; Ascorbic Acid; Carcinoma 256, Walker; Chondroitin; Fibroblasts; Heparin; Hyaluronoglucosaminidase; Hydrocortisone; In Vitro Techniques; Rats; Sarcoma, Experimental