Esculetin, a coumarin compound, was found to inhibit cell growth and cell cycle progression by inducing arrest of the G1 phase in HL-60 cells. To obtain information regarding cell cycle arrest induced by esculetin, we examined its effect on the regulating factors of the G1 phase in the leukemia HL-60 cells treated with esculetin by Western blotting. Our observations were: (1) a distinct increase in the level of hypophosphorylated retinoblastoma protein (pRb), and a reduction in the level of CDK4 after treatment with 100 microM of esculetin for 24 h; (2) a marked up-regulation of p27, and a down-regulation of cyclin D1 after treatment with 100 microM esculetin for 24 h. These results suggest that esculetin can inhibit the growth of human leukemia HL-60 cells by G1 phase cell cycle arrest as a result of inhibited pRb phosphorylation.
