Down-modulation of P210bcr/abl induces apoptosis/differentiation in K562 leukemic blast cells.
OBJECTIVE
K562 cells are growth factor independent and neither function as stem cells nor differentiate into functional end cells. They are blast cells. There is evidence that the constitutively expressed bcr-abl tyrosine kinase might be responsible for the maintenance of the blast state of CML cells. We have studied the effect of two tyrosine kinase inhibitors, quercetin and genistein, on K562 cells.


METHODS
K562 cells were treated with quercetin/genistein for a period of 72 hrs and then subjected to staining for apoptosis and erythroid differentiation and Western blotting with c-abl and phosphotyrosine monoclonal antibodies.


RESULTS
The IC50 value was found to be 9.2 micrograms/ml for quercetin and 11.8 micrograms/ml for genistein. Quercetin-treated cells did not show any differentiation but showed 68% apoptosis as compared to 7% in control. Genistein-treated cells showed 16% apoptosis and 15% erythroid differentiation. Quercetin reduced the level of p210 by 74% and its phosphotyrosine content by 67.6%. Genistein reduced p210 by 77.8% and its phosphotyrosine content by 16%.


CONCLUSIONS
Both quercetin and genistein are able to down-modulate the tyrosine kinase activity of p210 as well as bring about a decrease in the content of the protein with different effects: quercetin induced apoptosis while genistein brought about both differentiation and apoptosis.
Deora
A B
AB
Chemotherapy and Stem Cell Biology Division, Tata Memorial Center, Parel, Mumbai, India.
Miranda
M B
MB
Rao
S G
SG
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D019833:Genistein / Q000494:pharmacology*; D007942:Leukemia, Experimental / Q000473:pathology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011794:Quercetin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D011794:Quercetin; D019833:Genistein; D011505:Protein-Tyrosine Kinases