Effects of gossypol acetate on apoptosis in primary cultured cells from patients with lymphoid leukemia and its synergy with dexamethasone / 中国实验血液学杂志

ABSTRACT

To investigate the effects of gossypol acetate on apoptosis in primary cultured cells from patients with acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL) and its synergistic effect with dexamethasone. The apoptosis-inducing effect of gossypol acetate on primary cultured leukemia cells was analyzed by flow cytometry (FCM). The effect of gossypol acetate on survival rates of Raji cells and mononuclear cells (MNC) from normal bone marrow were evaluated by MTT assay. After co-treatment with gossypol acetate and dexamethasone, the apoptosis rate of Raji cells was detected by FCM. The results showed that gossypol acetate was able to induce apoptosis in primary cultured ALL cells at concentrations of ≥ 5 µmol/L. The effect was concentration and time dependent. Apoptosis-inducing concentration in CLL cells was higher than that in ALL cells. After exposing to 50 µmol/L gossypol acetate for 48 h, the apoptosis rate of ALL and CLL cells were (90.4 ± 6.2)% and (51.7 ± 10.3)% separately. No major growth inhibitory effect was observed in MNC from normal bone marrow when they were exposed to gossypol acetate at concentrations lower than 10 µmol/L. After exposing for 48 and 72 h, the IC(50) of gossypol acetate for MNC from normal bone marrow was 7.1 and 9.1 times as much as the IC(50) of Raji cells. Co-treatment with 10 µmol/L gossypol acetate and dexamethasone remarkably increased the apoptosis rate of Raji cells. It is concluded that the gossypol acetate has apoptosis-inducing activity in primary cultured leukemia cells from patients diagnosed as ALL and CLL in vitro. The inhibitory effect of gossypol acetate on MNC from normal bone marrow is less prominent than that on Raji cells. Co-treatment with gossypol acetate and dexamethasone notably amplified the pro-apoptosis activity of the latter in Raji cells.