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Current treatment practices of surgery and chemotherapy increase 1\u2010year survival by only 45%. The curcumin analogue RL71, has demonstrated potent in vitro and in vivo efficacy in several models of human breast cancer through increased apoptosis and cell cycle arrest. Thus, the present study aimed to investigate efficacy of curcumin analogues in two canine osteosarcoma cell lines. Osteosarcoma cell viability was assessed using the sulforhodamine B assay and mechanisms of action were determined by analysing the levels of cell cycle and apoptotic regulatory proteins via Western blotting. Further evidence was obtained using flow cytometry to detect cell cycle distribution and the number of apoptotic cells. RL71 was the most potent curcumin analogue with EC<jats:sub>50<\/jats:sub> values of 0.64\u2009\u00b1\u20090.04 and 0.38\u2009\u00b1\u20090.009\u2009\u03bcM (<jats:italic>n<\/jats:italic>\u2009=\u20093) in D\u201017 (commercial) and Gracie canine osteosarcoma cells, respectively. RL71 significantly increased the ratio of cleaved\u2010caspase 3 to pro\u2010caspase 3 and the level of apoptotic cells at the 2\u00d7 and 5\u00d7 EC<jats:sub>50<\/jats:sub> concentration (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001, <jats:italic>n<\/jats:italic>\u2009=\u20093). Furthermore, at the same concentration, RL71 significantly increased the number of cells in the G2\/M phase. In conclusion, RL71 has potent cytotoxic activity in canine osteosarcoma cells triggering G2\/M arrest and apoptosis at concentrations achievable in vivo. Future research should further investigate molecular mechanisms for these changes in other canine osteosarcoma cell lines prior to in vivo investigation.<\/jats:p>","DOI":"10.1111\/vco.12922","type":"journal-article","created":{"date-parts":[[2023,7,12]],"date-time":"2023-07-12T08:53:45Z","timestamp":1689152025000},"page":"595-604","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The second\u2010generation curcumin analogue <scp>RL71<\/scp> elicits <scp>G2<\/scp>\/<scp>M<\/scp> cell cycle arrest and apoptosis in canine osteosarcoma cells"],"prefix":"10.1111","volume":"21","author":[{"given":"Barnaby","family":"Kelly","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology University of Otago  Dunedin New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas","family":"Thamm","sequence":"additional","affiliation":[{"name":"Flint Animal Cancer Center Colorado State University  Ft. 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