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Role of Intracellular Calcium Ion in Human Promyelocytic Leukemia HL-60 Cell Differentiation¹

First Division, Department of Internal Medicine, Faculty of Medicine, Kyoto University, 54-Shogoin-kawaramachi, Sakyo-ku, Kyoto 606, Japan

The relationship between calcium ions and the differentiation of human promyelocytic leukemia HL-60 cells was investigated. Proliferation of HL-60 cells incubated in calcium-free medium was inhibited without cell differentiation. On the other hand, incubation with 100 µM verapamil markedly inhibited cell proliferation and caused slight cell differentiation into monocytes. Both calcium-free medium and 100 µM verapamil enhanced HL-60 cell differentiation after treatment with 1 nM 1,25-dihydroxyvitamin D₃, 1 nM ß-all-trans-retinoic acid, or 0.75% dimethyl sulfoxide. However, no enhancement was obtained by treatment with 1 nM 12-O-tetradecanoylphorbol-13-acetate.

The free cytosolic calcium concentration was measured by the intracellularly trappable fluorescent calcium indicator, quin 2. The increase of intracellular calcium induced by 250 nM ionomycin was completely blocked by 100 µM verapamil in calcium-free medium, suggesting that the high concentration of verapamil (100 µM) blocks the intracellular calcium mobilization in HL-60 cells.

Therefore, the enhancing effect of calcium deprivation or verapamil of HL-60 cell differentiation seemed to be closely related to the inhibition of intracellular calcium mobilization. This speculation is supported by the finding that 50 µM 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate, an intracellular calcium antagonist, also enhanced HL-60 cell differentiation induced by 1,25-dihydroxyvitamin D₃, ß-all-trans-retinoic acid, or dimethyl sulfoxide.

¹ This work was supported by Grants-in-Aid for Cancer Research from the Ministry of Education, Science and Culture.

² To whom requests for reprints should be addressed.

Received 4/14/86. Revised 7/22/86. Accepted 7/30/86.