Inhibition of differentiation of mouse myeloid leukemia cells by phenolic antioxidants and alpha-tocopherol.

Mouse myeloid leukemia cells (Ml) could be induced to differentiate into mature macrophages and granulocytes by treatment with dexamethasone or a protein induced in ascitic fluid from tumor-bearing rats. The effects of antioxidants (butyrated hydroxyanisole, butyrated hydroxytoluene, alpha-tocopherol, propyl gallate, disulfiram, cysteamine, ascorbate, selenite and glutathione) on differentiation of the cells were examined. Butyrated hydroxyanisole, butyrated hydroxytoluene and alpha-tocopherol significantly inhibited the differentiation of the cells induced by dexamethasone or a protein inducer. Other antioxidants had little or no inhibitory activity. Among the antioxidants tested, butyrated hydroxyanisole was the most potent inhibitor. The inhibition by butyrated hydroxyanisole was the most potent inhibitor. The inhibition by butyrated hydroxyanisole was not due to cytotoxicity and was reversible. The butyrated hydroxyanisole-mediated inhibition was counteracted by prostaglandin E1 or E2 but not F1 alpha. Moreover, butyrated hydroxyanisole inhibited the production of prostaglandin E2 by M1 cells treated with dexamethasone. These results suggest that the inhibition by butyrated hydroxyanisole of differentiation of M1 cells may be due to the inhibition of synthesis of prostaglandin E2.