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.

The influence of adult stem cells on tumor growth is paradoxical. On one hand, angiogenic factors secreted by stem cells are known to be essential for tumor vascularization. On the other hand, stem cell-derived factors can reportedly induce tumor differentiation or direct death of tumor cells. Both the placenta and umbilical cord are rich sources of stem cells with immune modulatory and tissue-healing properties; however, the effects of placental components on cancer cells have not been fully defined. Here we demonstrate that extracts of placental lysates reduce the malignancy of a variety of human tumor cell lines in a species-unrestricted manner. Using a standard model of leukemia cell differentiation, we demonstrated that addition of placental extracts to tumor cells, or co-culture of tumor cells with the CD34(+) cells from umbilical cord blood, induced tumor cell differentiation. Inhibition of tumor growth and metastasis in vivo was also observed following administration of placental extracts. These data support the concept of non-toxic biological therapy of cancer using stem cell derivatives, possibly through the induction of tumor cell differentiation.