Resistance to imatinib mesylate is an emergent problem in the treatment of Bcr-Abl expressing myelogenous leukemiasand additional therapeutic strategies are required. We observed that galangin, a non-toxic, naturally occurring flavonoidwas effective as anti-proliferative, and apoptotic agent in Bcr-Abl expressing K562 and KCL22 cells and in imatinib mesylateresistant K562-R and KCL22-R cells. Galangin induced an arrest of cells in G0–G1phase of cell cycle and a decreasein 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 bothin 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 interestingcandidate for a combination therapy in the treatment of imatinib-resistant leukemias.
|Number of pages||9|
|Publication status||Published - 2008|
All Science Journal Classification (ASJC) codes
- Cancer Research
Pipitone, R. M., Gebbia, N., Grimaudo, S., Meli, M., Dusonchet, L., Titone Lanza Di Scalea, L., Simoni, D., Di Cristina, A., & Invidiata, F. (2008). Galangin increases the cytotoxic activity of imatinib mesylate in imatinib-sensitive and imatinib-resistant Bcr-Abl expressing leukemia cells. Cancer Letters, 265, 289-297.