title: The radiosensitizing effect of the aurora kinase inhibitors, ENMD-2076, on canine mast cell tumours in vitro.
abstract: ENMD-2076 is an aurora kinase inhibitor that also has multi-target tyrosine kinase inhibitor properties. In this study, the mRNA and the protein expression of aurora-A and aurora-B were evaluated in three canine mast cell tumour cell lines. Dose-dependent cytotoxicity was seen in the cells treated, and it affected the cell cycle with cells in the G2/M phase being selectively killed. The cells were also evaluated for radiosensitivity with/without ENMD-2076, and radiosensitization was seen after 3 Gy and 6 Gy exposures with ENMD-2076 for 48 h. Protein expression of caspase-3 was gradually increased, and the expression intensity was highest at 24 h post irradiation in cells without ENMD-2076 treatment, which indicates that radiation exposure with ENMD-2076-induced cell death faster than radiation treatment alone. Our study results suggest the potential usefulness of treating canine mast cell tumours with aurora kinase inhibitors alone or in conjunction with radiation therapy.
authors.affiliation: Department of Veterinary Clinical Sciences, Cancer Treatment Unit, Louisiana State University, Baton Rouge, LA, USA.
authors.forename: K
authors.initials: K
authors.lastname: Shiomitsu
authors.affiliation: Department of Physics, Medical Physics Program, University of Massachusetts Lowell, Lowell, MA, USA.
authors.forename: E
authors.initials: E
authors.lastname: Sajo
authors.affiliation: Department of Veterinary Clinical Sciences, Cancer Treatment Unit, Louisiana State University, Baton Rouge, LA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Rubin
authors.affiliation: Department of Comparative Biomedical Sciences, Louisiana State University, Baton Rouge, LA, USA.
authors.forename: I
authors.initials: I
authors.lastname: Sehgal
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D064096:Aurora Kinase A / Q000235:genetics / Q000378:metabolism; D064107:Aurora Kinase B / Q000235:genetics / Q000378:metabolism; D064127:Aurora Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival; D004283:Dog Diseases / Q000188:drug therapy*; D004285:Dogs; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D034801:Mastocytoma / Q000628:therapy*; D011720:Pyrazoles / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D014964:X-Ray Therapy
chemical_list: C551397:ENMD 2076; D011720:Pyrazoles; D011743:Pyrimidines; D011838:Radiation-Sensitizing Agents; D064096:Aurora Kinase A; D064107:Aurora Kinase B; D064127:Aurora Kinases
keywords: ENMD-2076; aurora kinase inhibitors; canine mast cell tumours; radiosensitivity