Biological effects of phorbol esters on human leukemia cells

Objective To investigate the effects of phorbol esters 12-o-tetradecanoylophorbol-13-acetate (TPA), TPD, MBPD and APD on apoptosis and proliferation of human leukemia cell lines HL-60, Kasumi-1, U937, U937A/E, K562 and K562/AO2 cells, and its possible mechanisms. Methods HL-60, Kasumi-1, U937, U937A/E, K562 and K562/AO2 cells were treated with (5 nmol/ L, 10 nmol/L, 20 nmol/L, 50 nmol/L) TPA, TPD, MBPD and APD, respectively. CCK-8 was used to detect the inhibition rate of cell proliferation, and flow cytometry was used to detect the apoptosis. Results TPA, TPD, MBPD, APD could inhibit the proliferation of HL-60, Kasumi-1, U937, U937A/E, K562 and K562/AO2 with the 72 h inhibition rate of 70%, 50%, 80%, 80%, 75% and 50%, respectively, and no significant difference was found between different drugs. In addition, they could promote the apoptosis of HL-60, Kasumi-1, U937, U937A/E, K562 and K562/AO2, especially for the AML1/ETO fusion genes negative cells (P＜ 0.05). Conclusion TPA, and its derivatives-TPD, MBPD and APD can be used in the treatment of leukemia, and AML1/ETO fusion gene may inhibit the effect of phorbol esters on leukemia cells.