RRR‐α‐tocopheryl succinate modulation of human promyelocytic leukemia (HL‐60) cell proliferation and differentiation

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Abstract
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‐α‐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 μg/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 μg/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 chemo‐taxis, phagocytosis, or changes in the expression of the cell surf ace markers, CD11a and CD18. However, HL‐60 cells treated for 48 hours with TS (15 μg/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.