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

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• 作者：Manlio Tolomeo ; Stefania Grimaudo ; Antonietta Di Cristina ; Rosaria M. Pipitone ; Luisa Dusonchet ; Maria Meli ; Lucia Crosta ; Nicola Gebbia ; Francesco Paolo Invidiata ; Lucina Titone ; Daniele Simoni
• 关键词：Bcr-Abl ; Leukemia ; Apoptosis ; Imatinib ; Flavonoids
• 刊名：Cancer Letters
• 出版年：2008
• 出版时间：8 July 2008
• 年：2008
• 卷：265
• 期：2
• 页码：289-297
• 全文大小：420 K

文摘

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–G1phase of cell cycle and a decrease in pRb, cdk4, cdk1, cycline B levels; moreover, 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.