Down-Modulation of P210^bcr/abl Induces Apoptosis/Differentiation in K562 Leukemic Blast Cells

Abstract

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.

Protein Kinase Cι Activity Is Necessary for Bcr-Abl-mediated Resistance to Drug-induced Apoptosis

“…Our results with PKC are reminiscent of those described previously for Bcr-Abl, whose expression and tyrosine kinase activity is required for resistance of K562 cells to drug-induced apoptosis (5,10,(11)(12)(13)(14)(15). Indeed, although both HL60 and K562 cells express similar levels of PKC, the pattern of PKC activity in these cells during apoptotic stress is distinct.…”

“…The Bcr-Abl gene is the transforming activity responsible for CML (9), and the resistance of K562 cells to drug-induced apoptosis is conferred by Bcr-Abl (5,10,11). Thus, inhibition of Bcr-Abl tyrosine kinase activity using selective inhibitors (12)(13)(14)(15) or of Bcr-Abl expression using antisense oligonucleotides (16,17) leads to increased sensitivity of K562 cells to apoptosis induced by many drugs including taxol.…”

NPB001-05 inhibits Bcr-Abl kinase leading to apoptosis of imatinib-resistant cells

“…Imatinib induced inhibition of tyrosine kinase was observed only with the wild type Bcr-Abl cells and not with Bcr-Abl T315I mutant cell line. Down modulation of Bcr-Abl kinase activity induces apoptosis and cell death (63). Treatment with NPB001-05 induced apoptosis, as early as 24 hours of drug treatment, and a significant cell population was in this zone after 48 hours, measured by annexin-V staining.…”

Genistein ve STI571’in (Imatinib) Kronik Myeloblastik Losemide Etkili Sinyal Protein Duzeylerine Etkileri

“…BCR-ABL ifade eden hücrelerde STI571 etkinliği yüksek doz uygulandığında ve ancak 2-4 gün sonra ortaya çıkar (9). Genistein K562 hücrelerinde uzun dönem (72 saat) ve yüksek dozda uygulandığında BCR-ABL'nin tirozin kinaz aktivitesini düşürür ve protein miktarını azaltır (9,10).…”