ascorbic-acid and Lymphoma--T-Cell

The molecular basis of interaction of selected carotenoids and xanthophylls with ascorbic acid on cancer cells was studied to determine their anticancer effects.. Drug accumulation was measured in a human ABCB1 gene-transfected mouse lymphoma cell line and in a human lung cancer cell line by flow cytometry; furthermore, their anticancer effects were determined in mice in vivo.. Several carotenoids inhibited the multidrug resistance of cancer cells. Ascorbic acid improved the effect of certain xanthophylls, but the effect of capsanthin was not modified. Capsanthin had weak (12%) but capsorubin (85%) had a remarkable antiproliferative effect on A549 lung cancer cells. Capsorubin reduced immediate-early tumor antigen expression, while capsanthin was not effective. Capsorubin accumulates selectively in the nuclei of cancer cells.. The Authors suggest a special complex formation between membrane-bound capsorubin and ascorbic acid, which can be exploited in experimental chemotherapy.

Topics: Animals; Ascorbic Acid; ATP Binding Cassette Transporter 1; ATP-Binding Cassette Transporters; Cell Line, Tumor; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Drug Synergism; Humans; Lung Neoplasms; Lymphoma, T-Cell; Male; Mice; Mice, Inbred CBA; Neoplasms; Pancreatic Neoplasms; Transfection; Xanthophylls; Xenograft Model Antitumor Assays

Cyclophosphamide, an antineoplastic drug effective against a wide variety of cancers is cytotoxic to normal cells also. Ascorbic acid (vitamin C) at higher concentrations possesses cytotoxic effects and it can also enhance the cytotoxicity of 5-fluorouracil in a dose-dependent manner in mouse lymphoma. In the present study, effect of cyclophosphamide treatment alone and in combination with ascorbic acid in vivo on the ultrastructure and some biochemical changes in Dalton's lymphoma tumor cells were investigated. Cyclophosphamide treatment causes disappearance of cell membrane processes, thickening and reduction in the number of mitochondrial cristae as well as the manifestation of rounded shape of mitochondria. The combination treatment with ascorbic acid plus cyclophosphamide caused further changes in tumor cells showing disintegration in the cell surface membrane, disruption in the nuclear membrane and roundish mitochondria with reduction and disruption in the mitochondrial cristae. The observed ascorbic acid plus cyclophosphamide-mediated decrease in reduced glutathione (GSH) in tumor cells may play an important role in the antitumor activity of cyclophosphamide by weakening cellular antioxidant-mediated defense mechanism, thereby increasing tumor cell's susceptibility to cell death. The cyclophosphamide-mediated decrease in lactate dehydrogenase activity in tumor cells and simultaneous increase in ascites supernatant may possibly indicate alteration in the membrane permeability of tumor cells for lactate dehydrogenase as well as tumor cell injury. Further investigation should determine detailed mechanism(s) involved in cyclophosphamide-induced ultrastructural and biochemical changes in tumor cells.

Topics: Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Ascites; Ascorbic Acid; Cyclophosphamide; Female; Glutathione; L-Lactate Dehydrogenase; Lymphoma, T-Cell; Male; Mice; Microscopy, Electron, Transmission; Mitochondria; Neoplasm Transplantation; Tumor Cells, Cultured

Non-Hodgkin lymphomas incidence has increased more than 70% in last 25 years. Aggressiveness, higher relapse rate, and treatment complications pose significant barriers. Decreased food intake and side effects of treatments make cancer patients vulnerable to deficiency of essential nutrients such as vitamin C, lysine, and proline leading to the formation of weak extra cellular matrix susceptible to easy breakdown by matrix metalloproteinase enzymes. Inhibition of these enzymes has shown promise in stopping metastasis.. In this study, we investigated the effects of a specific nutrient mixture, containing ascorbic acid, lysine, proline, green tea extract among others, in most aggressive forms of non-Hodgkin's lymphoma - Burkitt's lymphoma, and T-cell lymphoma - using Raji and Jurkat cells respectively.. Nutrient mixture (NM) doses of 0, 10, 50, 100, 500, 1000 microg/ml, were used to study effects on cell proliferation, expression of matrix metalloproteinase, Matrigel invasion and apoptosis.. The results demonstrated that the dose response toxicity of the nutrient mixture on Raji cells gradually increased with increasing concentration. The nutrient mixture was non-toxic to Jurkat cells, however exhibited anti-proliferative properties at higher concentrations. Zymography demonstrated, NM had a significant inhibitory effect on matrix metalloproteinase-9 expression with total inhibition at 1000 microg/ml for Raji cells and at 500 microg/ml for Jurkat cells. The NM at 100 microg/ml completely inhibited Matrigel invasion for Raji cells, and at 1000 microg/ml for Jurkat cells. After the NM challenge virtually all Raji and Jurkat cells exposed to 1000 microg/ml were in late apoptosis.. Considering the lack of treatment options and continually increasing incidence, NM could be further explored for its therapeutic potential in Burkitt's lymphoma and T-cell lymphoma.

Topics: Antineoplastic Agents; Apoptosis; Ascorbic Acid; Burkitt Lymphoma; Cell Proliferation; Collagen; Drug Combinations; Humans; Laminin; Lymphoma, T-Cell; Lysine; Matrix Metalloproteinase 9; Neoplasm Invasiveness; Proline; Proteoglycans; Tea; Tumor Cells, Cultured

Analysis of cultured rat "Nb2 lymphoma" cell lines, showing different degrees of malignant progression, can lead to identification of phenotypic changes associated with this phenomenon in T-cell cancers. In the present study we have compared the metastatic sublines, Nb2-11 and Nb2-SFJCD1, with regard to ascorbate and glutathione recycling, important processes in cellular protection from oxidative stresses. Whereas the Nb2-11 subline is prolactin (PRL)-dependent, the genetically related Nb2-SFJCD1 subline is growth factor-independent and shows more chromosomal alterations, indicative of more advanced progression. The Nb2-SFJCD1 cells, compared to the Nb2-11 cells, were less sensitive to toxic effects of dehydroascorbate, a potentially toxic oxidation product of ascorbate. Results were consistent with a significantly higher production of reducing equivalents (e.g., NADPH, GSH) and an accelerated reduction of dehydroascorbate by homogenates of Nb2-SFJCD1 cells. However, the increased resistance was apparently not directly related to the cellular uptake and reduction of dehydroascorbate by whole cells, which was similar in both cell lines. Observations indicate that Nb2 lymphoma cells, in their progression to malignancy, can acquire an enhanced capability to protect themselves from oxidative damage assisting them in withstanding the oxidative stress that anti-neoplastic drugs can cause. The adaptation may also be a mechanism that is utilized by tumor cells in suppressing apoptosis and other protective cellular functions facilitating, or potentiating, a tumor cell's ability to become more metastatic. However, the mechanism leading to this augmented capacity of Nb2 lymphoma cells to resist oxidative stress in not known and is the subject for further study.

Topics: Animals; Apoptosis; Ascorbic Acid; Biological Transport, Active; Dehydroascorbic Acid; DNA Fragmentation; Glutathione; Lymphoma, T-Cell; NADP; Neoplasm Metastasis; Oxidative Stress; Phenotype; Rats; Tumor Cells, Cultured

1. Previously, we reported that calcium L-threonate caused a dose-related increase in uptake of ascorbic acid (AA) by human T-lymphoma cells. Preincubation of mouse fibroblasts with calcium L-threonate also resulted in a dose-related augmentation in uptake of AA as compared to non-treated controls. 2. Potassium L-lyxonate increased AA uptake by lymphoma cells, but did not significantly affect uptake by fibroblasts. Tartaric acid decreased uptake of AA by both cell lines. 3. Ouabain and dinitrophenol had no effect on AA uptake nor on the ability of threonate to augment AA uptake by fibroblasts. However, in T-lymphoma cells ouabain and dinitrophenol reduced AA uptake and prevented augmentation of AA uptake by calcium L-threonate.

Topics: 3T3 Cells; Animals; Ascorbic Acid; Butyrates; Humans; Lymphoma, T-Cell; Mice; Sugar Acids; Tumor Cells, Cultured

Little is known about dietary factors and non-Hodgkin's lymphoma (NHL) risk, although high intakes of animal protein and milk have been associated with NHL in two previous studies. As part of a population-based case-control study of agricultural and other risk factors for NHL in eastern Nebraska (USA), we examined the self- and proxy-reported frequency of consumption of 30 food items by 385 White men and women with NHL and 1,432 controls. Animal protein intake was not associated significantly with the risk of NHL, however, there was a nonsignificantly elevated risk of NHL among men with high milk consumption. Vitamin C, carotene, citrus fruit, and dark green vegetable intakes were inversely significantly related to the risk of NHL for men, but not for women. Among men, the odds ratios for the highest quartiles of both vitamin C and carotene intake were 0.6 (95% confidence intervals = 0.3-1.0). There were no meaningful differences in the associations of nutrient intakes and NHL risk between B- and T-cell lymphomas and histologic types. Risks for low intakes of vitamin C and carotene were greater among men and women with a family history of cancer, particularly a history of lymphatic or hematopoietic cancer among first-degree relatives.

Topics: Adult; Aged; Animal Population Groups; Animals; Ascorbic Acid; Carotenoids; Case-Control Studies; Citrus; Diet; Dietary Proteins; Female; Food; Humans; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell; Male; Middle Aged; Milk; Nebraska; Population Surveillance; Risk Factors; Sex Factors; Vegetables; White People

Vitamin C has been suggested and disputed as an anti-cancer agent. Previous in vitro studies using either primary cell cultures from cancer patients or tumor cell lines have suggested that tumor cells with different lineages may have different sensitivities to ascorbic acid. In this study we report characterization of the effects of ascorbic acid on growth of two ascorbic acid sensitive and one ascorbic acid resistant lymphocyte tumor cell lines. The cytotoxic effects of ascorbic acid on the sensitive cell lines were time and dosage dependent. Furthermore, the energy state of the ascorbic acid sensitive cells was affected by the presence of ascorbic acid before the cells became apparently non-viable, as demonstrated by 31P nuclear magnetic resonance spectroscopy. The existence of these lymphocyte cell lines with varying sensitivities to ascorbic acid may provide a useful model system for further understanding of vitamin C action on cancer cells.

Topics: Adenosine Triphosphate; Ascorbic Acid; Cell Division; Drug Resistance; Humans; Leukemia, B-Cell; Leukemia, T-Cell; Lymphocytes; Lymphoma, T-Cell; Magnetic Resonance Spectroscopy; Phosphorus; Tumor Cells, Cultured

The effects of preincubation of human T-lymphoma cells with increasing concentrations of calcium L-threonate on the uptake of L-[1-14C]ascorbic acid were examined. Calcium L-threonate (0-1,000 mg%) stimulated ascorbic acid (1.25 mg%) uptake in a dose-dependent manner. These results indicate that calcium threonate and possibly other ascorbic acid metabolites have biological activity and potential pharmacological applications.

Topics: Analysis of Variance; Ascorbic Acid; Butyrates; Dose-Response Relationship, Drug; Humans; Lymphoma, T-Cell; Tumor Cells, Cultured