INDUCTION OF HL-60 CELL-DIFFERENTIATION BY CAROTENOIDS

Recent observations indicated that carotenoids affected the proliferat ion and differentiation of certain cell lines. In the current experime nts, beta-carotene and lutein were tested for the induction of differe ntiation with HL-60 cells, a bipotent promyelocytic leukemia cell line . Cultures were incubated with lutein (0.0-10.0 mu mol/l), beta-carote ne (0.0-10.0 mu mol/l), and retinoic acid (0.0-1.0 mu mol/l); retinoic acid incubations were positive controls for the differentiation of HL -60 cells into granulocytes. The carotenoid-incubated cultures develop ed significantly more (p less than or equal to 0.05) differentiated ce lls than control cultures (vehicle alone). Morphology of the carotenoi d-incubated cells indicated differentiation along the granulocytic pat hway. The percentage of differentiated cells increased significantly t hroughout a seven-day incubation period to 25% (lutein), 35% (beta-car otene), and 75% (retinoic acid). A dose response was found for lutein (0.0-10.0 mu mol/l), bur not for beta-carotene. Throughout the incubat ion period, the percentage of differentiated cells in negative control cultures did not change, remaining at the initial background level (a pproximate to 5%). These results provide evidence for carotenoid-induc ed differentiation of cells. Induction of cell differentiation by a ca rotenoid without (lutein) and with (beta-carotene) vitamin A activity suggested a vitamin A-independent mode of action for carotenoids in ce ll differentiation.