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Doxorubicin and a butyric acid derivative effectively reduce levels of BCL‐2 protein
in the cells of chronic lymphocytic
leukemia patient
Author(s) -
Rabizadeh E.,
Bairey O.,
Aviram A.,
BenDror I.,
Shaklai M.,
Zimra Y.
Publication year - 2001
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1034/j.1600-0609.2001.066004263.x
Subject(s) - doxorubicin , apoptosis , chronic lymphocytic leukemia , cancer research , viability assay , leukemia , cell culture , butyric acid , biology , chemotherapy , medicine , immunology , chemistry , biochemistry , genetics
B‐chronic lymphocytic leukemia (B‐CLL) is a disease caused primarily by defects in the apoptosis mechanism. AN‐9, a butyric acid (BA) derivative, is a potent differentiating and an anti‐cancer drug that induces apoptosis in HL‐60 cells. Herein we show the affect of AN‐9, alone and in combination with doxorubicin, on cell cultures from B‐CLL patients. Cells from 17 patients were cultured and tested for viability, apoptosis, bcl‐2 and bax protein expression. Exposure of B‐CLL cell cultures to AN‐9 was accompanied by apoptosis and a marked viability loss (up to 46%, p =0.0017). AN‐9 reduced up to 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 than additively enhanced apoptosis and reduced bcl‐2 levels in B‐CLL cultures which were resistant to AN‐9. AN‐9 enhanced bax expression up to 58%( p =0.008) in cultures from 53% of the patients, but had no effect on bax levels when combined with doxorubicin. In conclusion, AN‐9 alone reduced bcl‐2 and enhanced bax expression in cultures 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.