Doxorubicin and a butyric acid derivative effectively reduce levels of BCL-2 protein in the cells of chronic lymphocytic leukemia patient

B-chronic lymphocytic leukemia (B-CLL) is a disease caused primarily by def ects in the apoptosis mechanism. AN-9, a butyric acid (BA) derivative, is a potent differentiating and an anti-cancer drug that induces apoptosis in H L-60 cells. Herein we show the affect of AN-9, alone and in combination wit h doxorubicin, on cell cultures from B-CLL patients. Cells from 17 patients were cultured and tested for viability, apoptosis, bcl-2 and bar protein e xpression. Exposure of B-CLL cell cultures to AN-9 was accompanied by apopt osis and a marked viability loss (up to 46%, p = 0.0017). AN-9 reduced up t o 51% (p = 0.0017) the levels of bcl-2 in 57% of the cultures that express bcl-2. The combination of low concentrations of AN-9 and doxorubicin more t han additively enhanced apoptosis and reduced bcl-2 levels in B-CLL culture s which were resistant to AN-9. AN-9 enhanced bar expression up to 58%(p = 0.008) in cultures from 53% of the patients, but had no effect on bar level s when combined with doxorubicin. In conclusion, AN-9 alone reduced bcl-2 and enhanced bar expression in cult ures from B-CLL patients, and the reduction of bcl-2 levels in combination with doxorubicin was greater than additive. These results may be beneficial in possible future combination therapy with AN-9 in B-CLL.