Identification of dasatinib as an in vitro potent growth inhibitor of canine histiocytic sarcoma cells

Canine histiocytic sarcoma (HS) is an aggressive and fatal neoplasm that has a high recurrence rate and metastatic nature. In the present report, compounds were screened for their growth inhibitory activity in two HS cell lines using a chemical library known to target specific signalling pathways. A...

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Bibliographic Details
Published in:The veterinary journal (1997) 2013-06, Vol.196 (3), p.536-540
Main Authors: Ito, Keita, Kuroki, Shiori, Kobayashi, Masato, Ono, Kenichiro, Washizu, Tsukimi, Bonkobara, Makoto
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
Canine histiocytic sarcoma
cell growth
Cell Line, Tumor
Cell lines
Compounds
Dasatinib
Dog Diseases - drug therapy
Dogs
growth retardation
Histiocytic Sarcoma - drug therapy
Indexing in process
inhibitory concentration 50
metastasis
phosphotransferases (kinases)
Pyrimidines - pharmacology
Pyrimidines - therapeutic use
sarcoma
Screening
signal transduction
Thiazoles - pharmacology
Thiazoles - therapeutic use
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Summary:Canine histiocytic sarcoma (HS) is an aggressive and fatal neoplasm that has a high recurrence rate and metastatic nature. In the present report, compounds were screened for their growth inhibitory activity in two HS cell lines using a chemical library known to target specific signalling pathways. Among 171 compounds screened, dasatinib, which targets several types of kinases, clearly inhibited cell growth in one of the two HS lines. The growth inhibitory properties of dasatinib were then examined using six HS cell lines and MDCK cells. Dasatinib demonstrated potent growth inhibitory activity against four HS cell lines with calculated IC50 values of 5.4–54.5nM, while the IC50 values in the other cell lines were in the micromolar range. In conclusion, a kinase enzyme targeted by dasatinib appears to be crucial for growth in some subsets of HS and the on-target activity of dasatinib could underlie the marked growth inhibition in HS cells.
ISSN:1090-0233
1532-2971
DOI:10.1016/j.tvjl.2012.12.016