ascorbic-acid and Sarcoma-180

Paclitaxel is used extensively as a chemotherapeutic agent against a broad range of tumors but often leads to the early termination of treatment due to severe toxic side effects. In this study, we hypothesized that ascorbic acid could reduce the toxic side effects without interfering with the anticancer effect of paclitaxel. To demonstrate this, we examined the effect of the combinational treatment of ascorbic acid and paclitaxel using H1299 (a non-small cell lung cancer cell line) and BALB/c mice implanted with or without sarcoma 180 cancer cells. In H1299 cells, the anticancer effects of the combinational treatment with paclitaxel and ascorbic acid were up to 1.7-foldhigher than those of single-agent paclitaxel treatment. In addition, it was shown that the viability of the HEL299 normal cells was up to 1.6-fold higher with the combinational treatment than with paclitaxel treatment alone. In vivo mouse experiments also showed that mice co-treated with paclitaxel and ascorbic acid did not exhibit the typical side effects induced by paclitaxel, such as a reduction in the numbers of white blood cells and red blood cells and the level of hemoglobin (P < .05). The analysis of cancer-related gene expression by quantitative real-time polymerase chain reaction and immunohistochemistry revealed that the combinational treatment suppressed cancer cell multiplication. Taken together, these results suggest that combinational chemotherapy with ascorbic acid and paclitaxel not only does not block the anticancer effects of paclitaxel but also alleviates the cytotoxicity of paclitaxel in vivo and in vitro.

Topics: Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Ascorbic Acid; Blood Cell Count; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Proliferation; Drug Synergism; Female; Gene Expression; Hemoglobins; Humans; Mice; Mice, Inbred BALB C; Paclitaxel; Sarcoma 180; Vitamins

Tumor cells have an invasive and metastatic phenotype that is the main cause of death for cancer patients. Tumor establishment and penetration consists of a series of complex processes involving multiple changes in gene expression. In this study, intraperitoneal administration of a high concentration of ascorbic acid inhibited tumor establishment and increased survival of BALB/C mice implanted with S-180 sarcoma cancer cells. To identify proteins involved in the ascorbic acid-mediated inhibition of tumor progression, changes in the liver proteome associated with ascorbic acid treatment of BALB/C mice implanted with S-180 were investigated using two-dimensional gel electrophoresis and mass spectrometry. Eleven protein spots were identified whose expression was different between control and ascorbic acid treatment groups. In particular, Raf kinase inhibitory protein (RKIP) and annexin A5 expression were quantitatively up-regulated. The increase in RKIP protein level was detected in the tumor tissue and accompanied by an increase in mRNA level. Our results suggest a possibility that these proteins are related to the ascorbic acid-mediated suppression of tumor formation.

Topics: Animals; Annexin A5; Antioxidants; Ascorbic Acid; Cell Line, Tumor; Humans; Liver; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Phosphatidylethanolamine Binding Protein; Proteome; Sarcoma 180; Survival Rate

Fullerenes have attracted considerable attention in recent years due to their unique chemical structure and potential applications. Hence it is of interest to study their biological effects. Using rat liver microsomes as model systems we have examined the ability of the most commonly used fullerene, C60 and its water-soluble derivative, C60(OH)18 to induce membrane damage on photosensitization. For photoexcitation, UV or tungsten lamps were used. Damage was assessed as lipid peroxidation products like conjugated dienes, lipid hydroperoxides and thiobarbituric acid reactive substances (TBARS). protein oxidation in the form of protein carbonyls, besides loss of membrane bound enzymes. Both fullerene derivatives induced significant oxidative damage. The alterations induced were both time- and concentration-dependent. Role of different reactive oxygen species (ROS) in the damage induced was examined by various scavengers of ROS and by deuteration of the buffer. The changes induced by C60 were predominantly due to 1O2 while that by C60(OH)18 was mainly due to radical species. Biological antioxidants such as glutathione, ascorbic acid and alpha-tocopherol were capable of inhibiting membrane damage induced by both the fullerenes. However, the damage induced by C60(OH)18 was more for both lipids and proteins than that showed by C60. C60 also showed enhancement in the formation of lipid peroxidation in sarcoma 180 ascites microsomes. In conclusion, our studies indicate that fullerene/its derivative can generate ROS on photoexcitation and can induce significant lipid peroxidation/protein oxidation in membranes and these phenomena can be prevented by endogenous/natural antioxidants.

Topics: Animals; Ascitic Fluid; Ascorbic Acid; Carbon; Dose-Response Relationship, Drug; Drug Antagonism; Fullerenes; Glutathione; Intracellular Membranes; Lipid Peroxidation; Microsomes, Liver; Models, Animal; Photosensitizing Agents; Rats; Reactive Oxygen Species; Sarcoma 180; Vitamin E

To determine the depth of permeation and concentration of HPD in tumor tissue which had been immersed in HPD in the presence and absence of ascorbic acid, and to examine its photosensitizing effect.. Solid S-180 sarcoma of 1 cm3 in size was excised from tumor-bearing mice and immersed in HPD (PsD-007) 1 mg/ml normal saline (group I), or HPD (PsD-007) 1 mg/ml plus ascorbic acid 20 mg/ml normal saline (group II) for 1 hr. For comparison, HPD (PsD-007) 10 mg/kg was injected intravenously to mice bearing tumor of similar size and the tumor was excised 24 hr later(group III).. When the tumors were cross-sectioned and UV (370 nm) irradiated, red fluorescence was mainly at the periphery of tumors that had been immersed in HPD whereas the fluorescence was weaker and more evenly distributed in tumors of mice that had received HPD i.v. Similar features were observed under fluorescence microscope in frozen sections of identically treated tumors. The concentration of PsD-007 (microgram/g) and malondialdehyde (nmol/L) in the tumor homogenates was higher in tumors that had been immersed in PsD-007 plus ascorbate than in tumors immersed in PsD-007 alone. Tumors of mice that had received PsD-007 i.v. had the lowest concentration of both PsD-007 and malondialdehyde.. Ascorbate facilitates permeation of HPD into tumor and enhances the photo-dynamic effect of HPD.

Topics: Animals; Ascorbic Acid; Drug Interactions; Free Radical Scavengers; Hematoporphyrin Photoradiation; Hematoporphyrins; Malondialdehyde; Mice; Photosensitizing Agents; Sarcoma 180

Immunological studies are reported showing that ascorbic acid, like selected sulfhydryl inhibitors, can induce immunity against some cancers in mice. Accompanying this immunizing action are changes in the surface structure of the cancer cells, as revealed by scanning electron microscopy. Electron spin resonance measurements show that the ascorbate anion free radical is readily produced in oxygenated cancer tissue and that this radical can react with sulfhydryl groups which are free radical scavengers. It is proposed that ascorbate acts as an effective thiolprive in oxygenated cancer tissues. This action is thought to lead to the observed changes in the cancer cell surface structure and to the concomitant immunological response.

Topics: Animals; Ascorbic Acid; Carcinoma, Ehrlich Tumor; Cell Line; Cell Membrane; Electron Spin Resonance Spectroscopy; Free Radicals; Mesothelioma; Mice; Microscopy, Electron, Scanning; Microvilli; Sarcoma 180; Sulfhydryl Reagents

Topics: Animals; Antineoplastic Agents; Ascorbic Acid; Carcinoma, Ehrlich Tumor; Epinephrine; Flavonoids; Lymphoma, Non-Hodgkin; Mice; Neoplasm Transplantation; Neoplasms, Experimental; Norepinephrine; Rats; Sarcoma 180

Topics: Animals; Ascorbic Acid; Binding Sites; Chromatography; Copper; Cytosine Nucleotides; DNA; Gluconates; Immunodiffusion; Ions; Ketones; Male; Mice; Neoplasm Transplantation; Nucleic Acids; Nucleotides; Pyrimidines; Sarcoma 180; Transplantation, Homologous