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. 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.
Department of Veterinary Clinical Pathology, Nippon Veterinary and Life Science University, 1-7-1 Kyonan-cho, Musashino-shi, Tokyo 180-8602, Japan.
Keita
K
Ito
Shiori
S
Kuroki
Masato
M
Kobayashi
Kenichiro
K
Ono
Tsukimi
T
Washizu
Makoto
M
Bonkobara
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D000069439:Dasatinib; D004283:Dog Diseases / Q000188:drug therapy*; D004285:Dogs; D054747:Histiocytic Sarcoma / Q000188:drug therapy*; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*; D013844:Thiazoles / Q000494:pharmacology / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D011743:Pyrimidines; D013844:Thiazoles; D000069439:Dasatinib