Galangin increases the cytotoxic activity of imatinib mesylate in imatinib-sensitive and imatinib-resistant Bcr-Abl expressing leukemia cells

被引：75

作者：

Tolomeo, Manlio ^{[1
]}

Grimaudo, Stefania ^{[1
]}

Di Cristina, Antonietta ^{[1
]}

Pipitone, Rosaria M. ^{[1
]}

Dusonchet, Luisa ^{[1
,2
]}

Meli, Maria ^{[1
,2
]}

Crosta, Lucia ^{[1
]}

Gebbia, Nicola ^{[1
]}

Invidiata, Francesco Paolo ^{[3
,5
]}

Titone, Lucina ^{[4
]}

Simoni, Daniele

机构：

[1] Univ Palermo, Oncol Clin, Ctr Interdipartimentale Ric, I-90127 Palermo, Italy

[2] Univ Palermo, Dipartimento Sci Farmacol, I-90127 Palermo, Italy

[3] Univ Palermo, Dipartimento Chim Farmaceut, I-90127 Palermo, Italy

[4] Univ Palermo, Dipartimento Malattie Infett, I-90127 Palermo, Italy

[5] Univ Ferrara, Dipartimento Chim Farmaceut, I-44100 Ferrara, Italy

来源：

CANCER LETTERS | 2008年 / 265卷 / 02期

关键词：

Bcr-Abl; leukemia; apoptosis; imatinib; flavonoids;

D O I：

10.1016/j.canlet.2008.02.025

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Resistance to imatinib mesylate is an emergent problem in the treatment of Bcr-Abl expressing myelogenous leukemias and additional therapeutic strategies are required. We observed that galangin, a non-toxic, naturally occurring flavonoid was effective as anti-proliferative, and apoptotic agent in Bcr-Abl expressing K562 and KCL22 cells and in imatinib mesylate resistant K562-R and KCL22-R cells. Galangin induced an arrest of cells in G0-G1 phase of cell cycle and a decrease in pRb, cdk4, cdk1, cycline B levels; morcover, it was able to induce a monocytic differentiation of leukemic Bcr-Abl+ cells. Of note, galangin caused a decrease in Bcl-2 levels and markedly increased the apoptotic activity of imatinib both in sensitive or imatinib-resistant Bcr-Abl+ cell lines. In contrast, flavonoids unable to modify the Bcl-2 intracellular levels, such as fisetin and chrysin, did not increase the apoptotic effect of imatinib. These data suggest that galangin is an interesting candidate for a combination therapy in the treatment of imatinib-resistant leukemias. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

引用

页码：289 / 297

页数：9

共 32 条

[1] Bcr-Abl exerts its antiapoptotic effect against diverse apoptotic stimuli through blockage of mitochondrial release of cytochrome c and activation of caspase-3 [J].