NOVEL ROLE OF VITAMIN-K-2 - A POTENT INDUCER OF DIFFERENTIATION OF VARIOUS HUMAN MYELOID-LEUKEMIA CELL-LINES

When myeloblastic ML1 cells were cultured in the presence of Vitamin K -2 (menaquinone, VK2), the population of cells capable of reducing NBT increased to 83.5% at low VK2 concentration of 1 mu M, indicating VK2 induces cellular differentiation. VK2 also exerted differentiation-in ducing action on histiocytic U937 and promyelocytic HL60 cell lines. N one of these effects were observed with Vitamin K-1 (phylloquinone, VK 1), suggesting the geranylgeranyl group of the side chain of VK2 to be essential to these effects. Combinations of VK2 with other differenti ation-inducers such as interferon-gamma retinoic acid, or camptothecin additively or synergistically induced the differentiation of HL-60 ce lls. These results suggest that VK2 may safely be used in differentiat ion therapy in combination with other inducers. (C) 1994 Academic Pres s, Inc.