Galangin increases the cytotoxic activity of imatinib mesylate in imatinib-sensitive and imatinib-resistant Bcr-Abl expressing leukemia cells
- Autori: Tolomeo, M.; Grimaudo, S.; DI CRISTINA, A.; Pipitone, R.; Dusonchet, L.; Meli, M.; Crosta, L.; Gebbia, N.; Invidiata, F.; TITONE LANZA DI SCALEA, L.; Simoni, D.
- Anno di pubblicazione: 2008
- Tipologia: Articolo in rivista (Articolo in rivista)
- Parole Chiave: Bcr-Abl; Leukemia; Apoptosis; Imatinib; Flavonoids
- OA Link: http://hdl.handle.net/10447/55699
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.