1. Galangin increases the cytotoxic activity of imatinib mesylate in imatinib-sensitive and imatinib-resistant Bcr-Abl expressing leukemia cells
- Author
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Nicola Gebbia, Stefania Grimaudo, Maria Meli, Daniele Simoni, Manlio Tolomeo, L. Crosta, Francesco Paolo Invidiata, Rosaria Maria Pipitone, Lucina Titone, Antonietta Di Cristina, Luisa Dusonchet, Tolomeo, M, Grimaudo, S, Di Cristina, A, Pipitone, RM, Dusonchet, L, Meli, M, Crosta, L, Gebbia, N, Invidiata, F, Titone Lanza di Scalea, L, and Simoni, D
- Subjects
Cancer Research ,Settore MED/17 - Malattie Infettive ,Settore MED/06 - Oncologia Medica ,Apoptosis ,Pharmacology ,Resting Phase, Cell Cycle ,Piperazines ,chemistry.chemical_compound ,Cell Line, Tumor ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Cytotoxic T cell ,Chrysin ,neoplasms ,Flavonoids ,Leukemia ,G1 Phase ,Apoptosi ,Cell Differentiation ,Imatinib ,medicine.disease ,Settore CHIM/08 - Chimica Farmaceutica ,Galangin ,Pyrimidines ,Imatinib mesylate ,Oncology ,chemistry ,Drug Resistance, Neoplasm ,Benzamides ,Settore BIO/14 - Farmacologia ,Imatinib Mesylate ,K562 Cells ,Fisetin ,Bcr-Abl ,K562 cells ,medicine.drug - Abstract
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.
- Published
- 2008