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.
Turley
J M
JM
Division of Nutritional Sciences, University of Texas, Austin 78712-1097.
Sanders
B G
BG
Kline
K
K
D015703:Antigens, CD / Q000187:drug effects; D000975:Antioxidants / Q000494:pharmacology; D002117:Calcitriol / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D008264:Macrophages / Q000187:drug effects; D009000:Monocytes / Q000187:drug effects; D011990:Receptors, Transferrin / Q000187:drug effects; D024505:Tocopherols; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology
D015703:Antigens, CD; D000975:Antioxidants; D011990:Receptors, Transferrin; D014810:Vitamin E; D014212:Tretinoin; D002117:Calcitriol; D024505:Tocopherols