RRR-alpha-tocopheryl succinate modulation of human promyelocytic leukemia (HL-60) cell proliferation and differentiation.

HL-60 human promyelocytic leukemia cells can be induced to differentiate to granulocytes by retinoic acid and dimethyl sulfoxide or monocyte-macrophages by phorbol esters and 1,25-dihydroxyvitamin D3. These studies show that RRR-alpha-tocopheryl succinate (TS) inhibits HL-60 cell proliferation and induces the HL-60 cells to differentiate toward a functionally deficient macrophage-like cell. TS at (15 micrograms/ml) was found to suppress HL-60 cell proliferation by 63% and 89% at 24 and 48 hours, respectively. This suppression of proliferation, however, is not permanent and requires the presence of TS. HL-60 cells treated for 48 hours with TS (15 micrograms/ml) were found to be blocked in the G2/M phase of the cell cycle. HL-60 cells blocked in the G2/M cell cycle phase by TS expressed normal levels of the transferrin receptor. TS-treated HL-60 cells exhibited binucleated morphological appearance; however, the cells did not exhibit chemotaxis, phagocytosis, or changes in the expression of the cell surface markers, CD11a and CD18. However, HL-60 cells treated for 48 hours with TS (15 micrograms/ml) could be stimulated to produce superoxide radicals and exhibited nonspecific esterase activity, two characteristics of macrophages. These results suggest a role for TS as an antitumor proliferative agent and as a modifier of human leukemia cell differentiation.