scholarly journals STI-571 Reports Bring New Hope to Cancer Treatment

2001 ◽  
Vol 23 (6) ◽  
pp. 44-46
Author(s):  
Naomi Pfeiffer
Keyword(s):  
Cancer Treatment ◽  
Sti 571

Inhibition of c-kit receptor tyrosine kinase activity by STI 571, a selective tyrosine kinase inhibitor

Blood ◽  
2000 ◽  
Vol 96 (3) ◽  
pp. 925-932 ◽  
Author(s):  
Michael C. Heinrich ◽  
Diana J. Griffith ◽  
Brian J. Druker ◽  
Cecily L. Wait ◽  
Kristen A. Ott ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Map Kinase ◽  
Cell Line ◽  
Cellular Proliferation ◽  
Kinase Activity ◽  
Leukemia Cell ◽  
Myelogenous Leukemia ◽  
Leukemia Cell Line ◽  
Tyrosine Kinase Activity ◽  
Sti 571

Abstract STI 571 (formerly known as CGP 57148B) is a known inhibitor of the c-abl, bcr-abl, and platelet-derived growth-factor receptor (PDGFR) tyrosine kinases. This compound is being evaluated in clinical trials for the treatment of chronic myelogenous leukemia. We sought to extend the activity profile of STI 571 by testing its ability to inhibit the tyrosine kinase activity of c-kit, a receptor structurally similar to PDGFR. We treated a c-kit expressing a human myeloid leukemia cell line, M-07e, with STI 571 before stimulation with Steel factor (SLF). STI 571 inhibited c-kit autophosphorylation, activation of mitogen-activated protein (MAP) kinase, and activation of Akt without altering total protein levels of c-kit, MAP kinase, or Akt. The concentration that produced 50% inhibition for these effects was approximately 100 nmol/L. STI 571 also significantly decreased SLF-dependent growth of M-07e cells in a dose-dependent manner and blocked the antiapoptotic activity of SLF. In contrast, the compound had no effect on MAP kinase activation or cellular proliferation in response to granulocyte-macrophage colony-stimulating factor. We also tested the activity of STI 571 in a human mast cell leukemia cell line (HMC-1), which has an activated mutant form of c-kit. STI 571 had a more potent inhibitory effect on the kinase activity of this mutant receptor than it did on ligand-dependent activation of the wild-type receptor. These findings show that STI 571 selectively inhibits c-kit tyrosine kinase activity and downstream activation of target proteins involved in cellular proliferation and survival. This compound may be useful in treating cancers associated with increased c-kit kinase activity.

Sti 571 induces caspase 9 and 3 dependent apoptosis of bcr-abl positive cells in-vitro; augmentation of apoptotic responses by trail

2000 ◽  
Vol 28 (7) ◽  
pp. 53 ◽  
Author(s):  
M.E. O'Dwyer ◽  
K.R. Rathbun ◽  
B.J. Druker ◽  
G.C. Bagby
Keyword(s):  
Caspase 9 ◽  
Sti 571

scholarly journals Combination therapy using TGF-β1 and STI-571 can induce apoptosis in BCR-ABL oncogene-expressing cells

2021 ◽  
Vol 12 (1) ◽  
pp. 144-155
Author(s):  
Masoome Bakhshayesh ◽  
Ladan Hosseini Gohari ◽  
Mahmood Barati ◽  
Majid Safa
Keyword(s):  
Combination Therapy ◽  
Tyrosine Kinase ◽  
Cell Signaling ◽  
Signaling Pathway ◽  
Kinase Inhibitor ◽  
K562 Cells ◽  
Parp Cleavage ◽  
Kinase Gene ◽  
Sti 571 ◽  
Tgf Β1

Abstract The BCR-ABL oncogene is a tyrosine kinase gene that is over-expressed in CML. It inhibits the TGF-β1 signaling pathway. Due to resistance of cells to the tyrosine kinase inhibitor, STI-571, the combined effect of STI-571 and TGF-β1 on K562 cells was studied in the present research. Results revealed that the TGF-β1 cell signaling pathway, which is activated in K562 cells treated with TGF-β1, activates collective cell signaling pathways involved in survival and apoptosis. It is noteworthy that treating K562 cells with STI-571 triggered apoptotic pathways, accompanied by a reduction in proteins such as Bcl-xL, Bcl-2, p-AKT, p-Stat5, p-FOXO3, and Mcl-1 and an increase in the pro-apoptotic proteins PARP cleavage, and p27, leading to an increase in sub-G1 phase-arrested and Annexin-positive cells. Interestingly, the proliferation behavior of TGF-β1-induced cells was changed with the combination therapy, and STI-571-induced apoptosis was also prompted by this combination. Thus, combination treatment appears to promote sub-G1 cell cycle arrest compared to individually treated cells. Furthermore, it strongly triggered apoptotic signaling. In conclusion, TGF-β1 did not negatively impact the effect of STI-571, based on positive annexin cells, and AKT protein phosphorylation remains effective in apoptosis.

scholarly journals Effect on Cell Cycle Progression by N-Myc Knockdown in SK-N-BE(2) Neuroblastoma Cell Line and Cytotoxicity with STI-571 Compound

2008 ◽  
Vol 40 (1) ◽  
pp. 27 ◽  
Author(s):  
Un-Young Yu ◽  
Je-Eun Cha ◽  
Sun-Young Ju ◽  
Kyung-Ah Cho ◽  
Eun-Sun Yoo ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Line ◽  
Cell Cycle Progression ◽  
Neuroblastoma Cell ◽  
Neuroblastoma Cell Line ◽  
Cycle Progression ◽  
Sti 571
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