Abstract

Inducing leukemia cell apoptosis is a major therapeutic strategy. Herein we investigate the enhancing effect of the herbal constituent parthenolide on aclarubicin-induced apoptosis of human HL-60 leukemia cells. HL-60 cells were incubated with aclarubicin in the absence or presence of different doses of parthenolide. Apoptosis was assessed by flow cytometry using annexin V-propidium iodide double staining. To investigate the molecular mechanism by which parthenolide enhances aclarubicin-induced HL-60 apoptosis, caspase 3 and caspase 9 expression, as well as Cox-2 and NF-κB activity, were assessed by western blot. Following exposure to aclarubicin for 20 h, the percentage of cells undergoing apoptosis was highly correlated with dose. However, there was no significant apoptosis at a low aclarubicin concentration (0.1 µg/ml). Combined treatment at low aclarubicin and parthenolide concentration had a dose-dependent effect on apoptosis. In addition, combined parthenolide and aclarubicin treatment had a significant synergistic inhibitory effect on caspase 3, caspase 9 and Cox-2, NF-κB activity. In conclusion, parthenolide sensitizes leukemia cells to aclarubicin-induced apoptosis through increasing expression of cleaved caspase 3 and caspase 9, maybe by suppress Cox-2 and NF-κB activation, suggesting a new avenue of treatment of leukemia.

Key words: Parthenolide, leukemia cells, apoptosis, NF-κB, Cox-2.