Combination of quercetin and Adriamycin effectively suppresses the growth of refractory acute leukemia.

ABSTRACT

The present study aimed to investigate the effect of combined treatment with quercetin and Adriamycin (doxorubicin) on the development of refractory acute leukemia. Primary leukemic cells were isolated from patients with refractory drug-resistant acute leukemia. The Cell Counting Kit-8 assay was used to detect the proliferation of cells treated with a range of doses of Adriamycin, quercetin and a combination of the two drugs. Non-irradiated mice were used to establish a T cell acute lymphoblastic leukemia (T-ALL) model, which was subsequently treated with Adriamycin, quercetin and a combination of the two drugs. The survival time was recorded, and white and red blood cells and platelets in mouse peripheral blood were counted. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) content of cardiac tissues were measured as indicators of oxidative stress and damage. Proliferation of primary leukemic cells was reduced by Adriamycin depending on the dose (0.06, 0.6 or 6 µg/ml) and treatment duration (24, 48 or 72 h) compared with the vehicle treated group. Co-treatment with quercetin achieved a similar suppression of leukemic cell proliferation when a lower dose of Adriamycin (0.03, 0.3 or 3 µg/ml) was administered for the same duration. The survival of non-irradiated mice with T-ALL was improved by co-treatment with a high dose of Adriamycin and quercetin compared with either treatment alone. Compared with treatment with Adriamycin alone, the combined treatment with Adriamycin and quercetin significantly enhanced the SOD activity and reduced the MDA content in the heart. Therefore, quercetin may enhance the effects of Adriamycin on refractory acute leukemia.