Induction of cell death by ascorbic acid derivatives in human renal carcinoma and glioblastoma cell lines

Sodium-L-ascorbate, L-ascorbic acid, D-isoascorbic acid, sodium 5,6-benzyli dene-L-ascorbate and sodium-6-beta-O-galactosyl-1-ascorbate, which produce ascorbyl radicals during the oxidative degradation, also induced cytotoxici ty against cultured human renal carcinoma (TC-1) and glioblastoma multiform tumor (T98G) cell lines. On the other hand, L-ascorbic acid 2-phosphate ma gnesium and L-ascorbic acid 2-sulfate dipotassium salt, which do not produc e the ascorbyl radical, were inactive. This-suggests the possible role of t he ascorbyl radical for cell death induction. T98G cells were more resistan t to ascorbate analogs than TC-I and HL-60 cells, possibly due to higher in tracellular glutathione concentrations. Ascorbate treatment induced rapid e levation of both intracellular concentration of cAMP and Ca2+ in HL-60 cell s, but not in TC-1 and T98G cells. However, the elevation of cAMP by theoph yline and N,2-dibutyryl adenosine 3,5 cyclic monophosphate (dibutyryl cAMP) resulted in a decrease in the viable cell number. This suggests the possib le role of cAMP for ascorbate-induced cell death.