Identification of anti-proliferative kinase inhibitors as potential therapeutic agents to treat canine osteosarcoma
Osteosarcoma is the most common primary bone tumour in dogs but various forms of therapy have not significantly improved clinical outcomes. As dysregulation of kinase activity is often present in tumours, kinases represent attractive molecular targets for cancer therapy. The purpose of this study wa...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2015
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| Online Access: | http://psasir.upm.edu.my/id/eprint/37916/1/Identification%20of%20anti-proliferative%20kinase%20inhibitors%20as%20potential%20therapeutic%20agents%20to%20treat%20canine%20osteosarcoma.pdf |
| _version_ | 1796973242142949376 |
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| author | Mauchle, Ulrike Selvarajah, Gayathri Thevi Mol, Jan A. Kirpensteijn, Jolle Verheije, Monique H. |
| author_facet | Mauchle, Ulrike Selvarajah, Gayathri Thevi Mol, Jan A. Kirpensteijn, Jolle Verheije, Monique H. |
| author_sort | Mauchle, Ulrike |
| collection | UPM |
| description | Osteosarcoma is the most common primary bone tumour in dogs but various forms of therapy have not significantly improved clinical outcomes. As dysregulation of kinase activity is often present in tumours, kinases represent attractive molecular targets for cancer therapy. The purpose of this study was to identify novel compounds targeting kinases with the potential to induce cell death in a panel of canine osteosarcoma cell lines. The ability of 80 well-characterized kinase inhibitor compounds to inhibit the proliferation of four canine osteosarcoma cell lines was investigated in vitro. For those compounds with activity, the mechanism of action and capability to potentiate the activity of doxorubicin was further evaluated. The screening showed 22 different kinase inhibitors that induced significant anti-proliferative effects across the four canine osteosarcoma cell lines investigated. Four of these compounds (RO 31-8220, 5-iodotubercidin, BAY 11-7082 and an erbstatin analog) showed significant cell growth inhibitory effects across all cell lines in association with variable induction of apoptosis. RO 31-8220 and 5-iodotubercidin showed the highest ability to potentiate the effects of doxorubicin on cell viability. In conclusion, the present study identified several potent kinase inhibitors targeting the PKC, CK1, PKA, ErbB2, mTOR and NF-κB pathways, which may warrant further investigations for the treatment of osteosarcoma in dogs. |
| first_indexed | 2024-03-06T08:39:45Z |
| format | Article |
| id | upm.eprints-37916 |
| institution | Universiti Putra Malaysia |
| language | English |
| last_indexed | 2024-03-06T08:39:45Z |
| publishDate | 2015 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | upm.eprints-379162015-12-29T09:43:02Z http://psasir.upm.edu.my/id/eprint/37916/ Identification of anti-proliferative kinase inhibitors as potential therapeutic agents to treat canine osteosarcoma Mauchle, Ulrike Selvarajah, Gayathri Thevi Mol, Jan A. Kirpensteijn, Jolle Verheije, Monique H. Osteosarcoma is the most common primary bone tumour in dogs but various forms of therapy have not significantly improved clinical outcomes. As dysregulation of kinase activity is often present in tumours, kinases represent attractive molecular targets for cancer therapy. The purpose of this study was to identify novel compounds targeting kinases with the potential to induce cell death in a panel of canine osteosarcoma cell lines. The ability of 80 well-characterized kinase inhibitor compounds to inhibit the proliferation of four canine osteosarcoma cell lines was investigated in vitro. For those compounds with activity, the mechanism of action and capability to potentiate the activity of doxorubicin was further evaluated. The screening showed 22 different kinase inhibitors that induced significant anti-proliferative effects across the four canine osteosarcoma cell lines investigated. Four of these compounds (RO 31-8220, 5-iodotubercidin, BAY 11-7082 and an erbstatin analog) showed significant cell growth inhibitory effects across all cell lines in association with variable induction of apoptosis. RO 31-8220 and 5-iodotubercidin showed the highest ability to potentiate the effects of doxorubicin on cell viability. In conclusion, the present study identified several potent kinase inhibitors targeting the PKC, CK1, PKA, ErbB2, mTOR and NF-κB pathways, which may warrant further investigations for the treatment of osteosarcoma in dogs. Elsevier 2015-08 Article PeerReviewed application/pdf en http://psasir.upm.edu.my/id/eprint/37916/1/Identification%20of%20anti-proliferative%20kinase%20inhibitors%20as%20potential%20therapeutic%20agents%20to%20treat%20canine%20osteosarcoma.pdf Mauchle, Ulrike and Selvarajah, Gayathri Thevi and Mol, Jan A. and Kirpensteijn, Jolle and Verheije, Monique H. (2015) Identification of anti-proliferative kinase inhibitors as potential therapeutic agents to treat canine osteosarcoma. The Veterinary Journal, 205 (2). pp. 281-287. ISSN 1090-0233; ESSN: 1532-2971 http://www.sciencedirect.com/science/article/pii/S109002331400327X 10.1016/j.tvjl.2014.08.006 |
| spellingShingle | Mauchle, Ulrike Selvarajah, Gayathri Thevi Mol, Jan A. Kirpensteijn, Jolle Verheije, Monique H. Identification of anti-proliferative kinase inhibitors as potential therapeutic agents to treat canine osteosarcoma |
| title | Identification of anti-proliferative kinase inhibitors as potential therapeutic agents to treat canine osteosarcoma |
| title_full | Identification of anti-proliferative kinase inhibitors as potential therapeutic agents to treat canine osteosarcoma |
| title_fullStr | Identification of anti-proliferative kinase inhibitors as potential therapeutic agents to treat canine osteosarcoma |
| title_full_unstemmed | Identification of anti-proliferative kinase inhibitors as potential therapeutic agents to treat canine osteosarcoma |
| title_short | Identification of anti-proliferative kinase inhibitors as potential therapeutic agents to treat canine osteosarcoma |
| title_sort | identification of anti proliferative kinase inhibitors as potential therapeutic agents to treat canine osteosarcoma |
| url | http://psasir.upm.edu.my/id/eprint/37916/1/Identification%20of%20anti-proliferative%20kinase%20inhibitors%20as%20potential%20therapeutic%20agents%20to%20treat%20canine%20osteosarcoma.pdf |
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