Cotylenin A-induced differentiation is independent of the transforming growth factor-β signaling system in human myeloid leukemia HL-60 cells

Abstract

Cotylenin A, which has been isolated as a plant growth regulator, potently induces the differentiation of human myeloid leukemia cells. Treatment of HL-60 cells with a combination of transforming growth factor (TGF)-β and 1α, 25-dihydroxyvitamin D₃ (VD3) resulted in increased differentiation compared to separate treatments, but TGF-β did not affect the cotylenin A-induced differentiation of HL-60 cells. It is possible that the signal transduction pathway used by cotylenin A for inducing the differentiation of leukemia cells is the same as that used by TGF-β. However, cotylenin A did not affect the expression of TGF superfamily or Smad genes in HL-60 cells. Treatment with neutralizing anti-TGF-β antibody or an inhibitor of TGF-β signaling did not inhibit cotylenin A-induced differentiation, although VD3-induced differentiation was significantly suppressed by these treatments. The subcellular distribution of Smad3 was also unaffected by cotylenin A. These results suggest that the cotylenin A-induced differentiation of leukemia cells is independent of the TGF-β signaling system, although TGF-β acts as an autocrine mediator of the growth arrest and differentiation of leukemia cells induced by VD3 and other inducers.

Keywords:

• Cotylenin A
• vitamin D3
• transforming growth factor-β
• Smad
• differentiation
• myeloid leukemia
• HL-60