Capsaicin potentiates 1,25-dihydoxyvitamin D-3- and all-trans retinoic acid-induced differentiation of human promyelocytic leukemia HL-60 cells

Human promyelocytic leukemia HL-60 cells are differentiated into monocytic or granulocytic lineage when treated with 1,25-dihydroxyvitamin D-3 [1,25-( OH)(2)D-3] or all-trans retinoic acid, respectively. In this study, the eff ect of capsaicin, an active component of the red pepper of the genus Capsoc um, on cell differentiation was investigated in a HL-60 cell culture system . Treatment of HL-60 cells with 5-30 mug/ml capsaicin for 72 h inhibited ce ll proliferation and induced a small increase in cell differentiation. Inte restingly, synergistic induction of HL-60 cell differentiation was observed when capsaicin was combined with either 5 nM 1,25-(OH)(2)D-3 or 50 nM all- trans retinoic acid. Row cytometric analysis indicated that combinations of 1,25-(OH)(2)D-3 and capsaicin stimulated differentiation predominantly to monocytes whereas combinations of all-trans retinoic acid and capsaicin sti mulated differentiation predominantly to granulocytes. Capsaicin enhanced p rotein kinase C activity in 1,25-(OH)(2)D-3- and all-trans retinoic acid-tr eated HL-60 cells. In addition, inhibitors for protein kinase C [bisindolyl maleimide (GF-109203X), chelerythrine, 1-(5-isoquinolinesulfonyl)-2-methylp iperazine dihydrochloride (H-7)] and an inhibitor for extracellular signal- regulated kinase [2-(2'-amino-3'-methosyphenyl)-oxanaphthalen-4-one (PD-098 059)] significantly inhibited HL-60 cell differentiation induced by capsaic in in combination with either 1,25-(OH)(2)D-3 or all-trans retinoic acid. T hese results indicate that capsaicin potentiates 1,25-(OH)(2)D-3- or all-tr ans retinoic acid-induced HL-60 cell differentiation and that both protein kinase C and extracellular signal-regulated kinase are involved in the cell differentiation synergistically enhanced by capsaicin. (C) 2001 Elsevier S cience B.V. All rights reserved.