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Because new metallodrugs are synthesized at high rates, our studies included assays in zebrafish to expedite the initial evaluation as anticancer agents. Here we evaluated novel metallodrugs (PMC79 and LCR134), and cisplatin, a widely used platinum-based chemotherapeutic. We hypothesized that this model could characterize anticancer properties and recapitulate previous in vitro results in vivo. Our findings suggest anticancer properties of PMC79 and LCR134 were similar with less toxicity than cisplatin. Exposures from 24 to 72\u2009h at or below the LOAELs of PMC79 and LCR134 (3.9\u2009\u00b5M and 13.5\u2009\u00b5m, respectively), impaired blood vessel development and tailfin regeneration. Blood vessel examination through live imaging of larvae revealed distinct regional antiangiogenic impacts. The significant decrease in gene expression of the VEGF-HIF pathway and beta-actin could explain the morphological effects observed in the whole organism following exposure. Tailfin amputation in larvae exposed to PMC79 or LCR134 inhibited tissue regrowth and cell division, but did not impact normal cell proliferation unlike cisplatin. This suggests Ru drugs may be more selective in targeting cancerous cells than cisplatin. Additionally, in vitro mechanisms were confirmed. PMC79 disrupted cytoskeleton formation in larvae and P-glycoprotein transporters in vivo was inhibited at low doses which could limit off-target effects of chemotherapeutics. Our results demonstrate the value for using the zebrafish in metallodrug research to evaluate mechanisms and off-target effects. In light of the findings reported in this article, future investigation of PMC79 and LCR134 are warranted in higher vertebrate models.<\/jats:p>","DOI":"10.1093\/toxsci\/kfab041","type":"journal-article","created":{"date-parts":[[2021,4,2]],"date-time":"2021-04-02T03:14:42Z","timestamp":1617333282000},"page":"29-43","source":"Crossref","is-referenced-by-count":13,"title":["Anticancer Activity and In Vitro to In Vivo Mechanistic Recapitulation of Novel Ruthenium-Based Metallodrugs in the Zebrafish Model"],"prefix":"10.1093","volume":"182","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1738-7235","authenticated-orcid":false,"given":"Brittany F","family":"Karas","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Microbiology, Rutgers University, New Brunswick, New Jersey 08854, USA"}]},{"given":"Jordan M","family":"Hotz","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Microbiology, Rutgers University, New Brunswick, New Jersey 08854, USA"},{"name":"Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA"}]},{"given":"Brian M","family":"Gural","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Microbiology, Rutgers University, New Brunswick, New Jersey 08854, USA"}]},{"given":"Kristin R","family":"Terez","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Microbiology, Rutgers University, New Brunswick, New Jersey 08854, USA"}]},{"given":"Victoria L","family":"DiBona","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Microbiology, Rutgers University, New Brunswick, New Jersey 08854, USA"}]},{"given":"Leonor","family":"C\u00f4rte-Real","sequence":"additional","affiliation":[{"name":"Centro de Qu\u00edmica Estrutural and Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universidade de Lisboa, Lisboa 1749-016, Portugal"}]},{"given":"Andreia","family":"Valente","sequence":"additional","affiliation":[{"name":"Centro de Qu\u00edmica Estrutural and Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universidade de Lisboa, Lisboa 1749-016, Portugal"}]},{"given":"Brian T","family":"Buckley","sequence":"additional","affiliation":[{"name":"Environmental and Occupational Health Sciences Institute, Rutgers University, Piscataway, New Jersey 08854, USA"}]},{"given":"Keith R","family":"Cooper","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Microbiology, Rutgers University, New Brunswick, New Jersey 08854, USA"}]}],"member":"286","published-online":{"date-parts":[[2021,4,3]]},"reference":[{"key":"2021071619492702900_kfab041-B1","doi-asserted-by":"crossref","first-page":"772","DOI":"10.2174\/1389557515666151001142012","article-title":"Ruthenium complexes: An emerging ground to the development of metallopharmaceuticals for cancer therapy","volume":"16","author":"Abid","year":"2016","journal-title":"Mini Rev. 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