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

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Rabizadeh E, Bairey O, Aviram A, Ben-Dror I, Shaklai M, Zimra Y

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

Eur J Haematol. 2001 Apr;66(4):263-71. doi: 10.1034/j.1600-0609.2001.066004263.x.

PubMed ID

11380606 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
AN-9	Apoptosis regulator Bcl-2	Protein	Humans	Yes	Downregulator	Details