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Galangin increases the cytotoxic activity of imatinib mesylate in imatinib-sensitive and imatinib-resistant Bcr-Abl expressing leukemia cells
- Source :
- Cancer Letters. 265:289-297
- Publication Year :
- 2008
- Publisher :
- Elsevier BV, 2008.
-
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.
- 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
Subjects
Details
- ISSN :
- 03043835
- Volume :
- 265
- Database :
- OpenAIRE
- Journal :
- Cancer Letters
- Accession number :
- edsair.doi.dedup.....8fad6861b9993c37bf11e791f47659ff