OBJECTIVE: To find out the mechanisms of redifferentiation and reversion of malignant human gastric cancer cells induced by ascorbic acid. METHODS: Human gastric cancer cells grown in the laboratory were used. The Trypan blue dye exclusion method was used to determine the cell doubling time. The electrophoresis rate and colonogenic potential were the indices used to measure the rate of redifferentiation. The content of malondialdehyde (MDA) was measured using the thiobarbituric acid (TBA) method. The activities of superoxide dismutase (SOD), catalase (CAT) and the content of H202 were evaluated by spectrophotography. RESULTS: Six mmol/L ascorbic acid was used as a positive control. Human gastric cancer cells were treated with 75 microm hydrogen peroxide, which alleviated many of the malignant characteristics. For example, the cell surface charge obviously decreased and the electrophoresis rate dropped from 2.21 to 1.10 microm x s(-1) x V(-1) x cm(-1). The colonogenic potential, a measure of cell differentiation, decreased 90.2%. After treatment with ascorbic acid, there was a concentration- and time-dependent increase in hydrogen peroxide (H202) and the activity of superoxide dismutase (SOD). However, the activity of catalase (CAT) resulted in a concentration- and time-dependent decrease. SOD and 3-amino-1,2,4-triazole (AT) exhibited some effects, but there were statistically significant differences between the SOD and AT group and the H202 group. CONCLUSIONS: Ascorbic acid induces growth inhibition and redifferentiation of human gastric cancer cells through the production of hydrogen peroxide.

Human pharmacokinetics data indicate that i.v. ascorbic acid (ascorbate) in pharmacologic concentrations could have an unanticipated role in cancer treatment. Our goals here were to test whether ascorbate killed cancer cells selectively, and if so, to determine mechanisms, using clinically relevant conditions. Cell death in 10 cancer and 4 normal cell types was measured by using 1-h exposures. Normal cells were unaffected by 20 mM ascorbate, whereas 5 cancer lines had EC(50) values of <4 mM, a concentration easily achievable i.v. Human lymphoma cells were studied in detail because of their sensitivity to ascorbate (EC(50) of 0.5 mM) and suitability for addressing mechanisms. Extracellular but not intracellular ascorbate mediated cell death, which occurred by apoptosis and pyknosis/necrosis. Cell death was independent of metal chelators and absolutely dependent on H(2)O(2) formation. Cell death from H(2)O(2) added to cells was identical to that found when H(2)O(2) was generated by ascorbate treatment. H(2)O(2) generation was dependent on ascorbate concentration, incubation time, and the presence of 0.5-10% serum, and displayed a linear relationship with ascorbate radical formation. Although ascorbate addition to medium generated H(2)O(2), ascorbate addition to blood generated no detectable H(2)O(2) and only trace detectable ascorbate radical. Taken together, these data indicate that ascorbate at concentrations achieved only by i.v. administration may be a pro-drug for formation of H(2)O(2), and that blood can be a delivery system of the pro-drug to tissues. These findings give plausibility to i.v. ascorbic acid in cancer treatment, and have unexpected implications for treatment of infections where H(2)O(2) may be beneficial.

OBJECTIVE: To explore the effects and mechanisms of ascorbic acid (AA) and sodium selenite (SS) on growth inhibition and redifferentiation in human gastric cancer cells. METHODS: In the present study, trypan blue dye exclusion method was used to determine the cell growth curve and mitotic index, cell electrophoresis and colonogenic potential were used as the indexes of redifferentiation. In order to find out the mechanisms of redifferentiation, the activities of superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase (CAT) were assayed, the content of malondialdehyde (MDA), reduced glutathione (GSH) and H2O2 were evaluated. RESULTS: After treatment with AA 3 mol/L + SS 2 mu mol/L, the growth rate and mitotic index of human gastric cancer cells (MGc-803) decreased remarkably. The indexes related with cell malignancy were alleviated. For example, cell surface charge was obviously decreased, the electrophoresis rate was dropped from 2.21 to 1.15 mu m.s-1.V-1.cm-1. The indexes related with cell redifferentiation were promoted. For example, the colonogenic potential was decreased to 93.5%. These results indicated that redifferentiation of human gastric cancer cells was successfully induced by AA + SS. The activities of SOD and GPX were significantly higher, while the activity of CAT was slower in treated group than that in the control. The content of MDA was slightly decreased, GSH was sharply decreased, and H2O2 content was dramatically increased. CONCLUSION: These results indicated that combination of ascorbic acid and sodium selenite may induce the redifferentiation of human gastric cancer cells and inhibit cell growth by virtue of enhancing the activities of antioxidative enzymes and inducing the formation of H2O2, and altering the cell redox status. Combination of ascorbic acid and sodium selenite may be a potent anticancer agent for human gastric cancer.

The effect of H2O2 on adenovirus types 3 and 6, adenoassociated virus type 4, rhinoviruses 1A, 1B, and type 7, myxoviruses, influenza A and B, respiratory syncytial virus, strain Long, and coronavirus strain 229E was studied in vitro, using different H2O2 concentration and timec of exposure. H2O2 in a 3 percent concentration inactivated all the viruses under study within 1--30 min. Coronavirus and influenza viruses were found to be most sensitive. Reoviruses, adenoviruses and adenoassociated virus were relatively stable. H2O2 is a convenient means for virus inactivation.