Capsaicin Potentiates 1,25-dihydoxyvitamin D3- And All-Trans Retinoic Acid-Induced Differentiation of Human Promyelocytic Leukemia HL-60 Cells

Eur J Pharmacol. 2001 May 25;420(2-3):83-90. doi: 10.1016/s0014-2999(01)00994-3.


Human promyelocytic leukemia HL-60 cells are differentiated into monocytic or granulocytic lineage when treated with 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] or all-trans retinoic acid, respectively. In this study, the effect of capsaicin, an active component of the red pepper of the genus Capsocum, on cell differentiation was investigated in a HL-60 cell culture system. Treatment of HL-60 cells with 5-30 microg/ml capsaicin for 72 h inhibited cell proliferation and induced a small increase in cell differentiation. Interestingly, synergistic induction of HL-60 cell differentiation was observed when capsaicin was combined with either 5 nM 1,25-(OH)2D3 or 50 nM all-trans retinoic acid. Flow cytometric analysis indicated that combinations of 1,25-(OH)2D3 and capsaicin stimulated differentiation predominantly to monocytes whereas combinations of all-trans retinoic acid and capsaicin stimulated differentiation predominantly to granulocytes. Capsaicin enhanced protein kinase C activity in 1,25-(OH)2D3- and all-trans retinoic acid-treated HL-60 cells. In addition, inhibitors for protein kinase C [bisindolylmaleimide (GF-109203X), chelerythrine, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7)] and an inhibitor for extracellular signal-regulated kinase [2-(2'-amino-3'-methoxyphenyl)-oxanaphthalen-4-one (PD-098059)] significantly inhibited HL-60 cell differentiation induced by capsaicin in combination with either 1,25-(OH)2D3 or all-trans retinoic acid. These results indicate that capsaicin potentiates 1,25-(OH)2D3- or all-trans 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / pharmacology
  • Alkaloids
  • Benzophenanthridines
  • Calcitriol / pharmacology*
  • Capsaicin / pharmacology*
  • Cell Differentiation / drug effects*
  • Cell Division / drug effects
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Enzyme Inhibitors / pharmacology
  • Flavonoids / pharmacology
  • HL-60 Cells / cytology
  • HL-60 Cells / drug effects
  • Humans
  • Indoles / pharmacology
  • Maleimides / pharmacology
  • Phenanthridines / pharmacology
  • Protein Kinase C / antagonists & inhibitors
  • Signal Transduction / drug effects
  • Tretinoin / pharmacology*


  • Alkaloids
  • Benzophenanthridines
  • Enzyme Inhibitors
  • Flavonoids
  • Indoles
  • Maleimides
  • Phenanthridines
  • Tretinoin
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • chelerythrine
  • Protein Kinase C
  • Calcitriol
  • bisindolylmaleimide I
  • Capsaicin
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one