Selective growth inhibition by suppression of F1Fo ATPase in canine malignant melanoma cell lines |
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| Authors: | S. Kuroki M. Kobayashi H. Tani R. Miyamoto S. Kurita K. Tamura K. Ono T. Washizu M. Bonkobara |
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| Affiliation: | 1. Department of Veterinary Clinical Pathology, Nippon Veterinary and Life Science University, Musashino‐shi, Tokyo, Japan;2. Japan Animal Referral Medical Center, Takatsu‐ku, Kawasaki‐shi, Kanagawa, Japan |
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| Abstract: | Canine malignant melanoma (CMM) is a highly aggressive and fatal neoplasm. To identify potential therapeutic compounds and/or targets, 320 compounds were screened for their growth inhibitory activity in a CMM line (CMM‐1) using a chemical library known to target specific signaling pathways/cell growth‐related molecules. Among the compounds screened, the F1Fo ATPase inhibitor oligomycin showed potent growth inhibitory effects in CMM‐1 cells, while exhibiting less toxic effects in a non‐neoplastic control cell line (MDCK cells). The growth inhibitory effect of oligomycin A was then examined using six CMM lines and MDCK cells. Three CMM lines were highly sensitive to oligomycin A, with around 3000–20 000 times lower IC50 compared with oligomycin A‐resistant CMM lines and MDCK cells. Oligomycin A‐sensitive CMM‐1 cells exhibited much greater oligomycin A‐induced decreases in cellular ATP compared to oligomycin A‐resistant cell lines. Although the oligomycins are clinically unsuitable because of its in vivo toxicity, these findings implicate the potential of F1Fo ATPase as a therapeutic target in a subset of CMM. |
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