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Ternary copper(II) complex: NCI60 screening, toxicity studies, and evaluation of efficacy in xenograft models of nasopharyngeal carcinoma

Copper(II) ternary complex, [Cu(phen)(C-dmg)(H(2)O)]NO(3) was evaluated against a panel of cell lines, tested for in vivo efficacy in nasopharyngeal carcinoma xenograft models as well as for toxicity in NOD scid gamma mice. The Cu(II) complex displayed broad spectrum cytotoxicity against multiple ca...

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Detalles Bibliográficos
Autores principales: Ahmad, Munirah, Suhaimi, Shazlan-Noor, Chu, Tai-Lin, Abdul Aziz, Norazlin, Mohd Kornain, Noor-Kaslina, Samiulla, D. S., Lo, Kwok-Wai, Ng, Chew-Hee, Khoo, Alan Soo-Beng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5766233/
https://www.ncbi.nlm.nih.gov/pubmed/29329342
http://dx.doi.org/10.1371/journal.pone.0191295
Descripción
Sumario:Copper(II) ternary complex, [Cu(phen)(C-dmg)(H(2)O)]NO(3) was evaluated against a panel of cell lines, tested for in vivo efficacy in nasopharyngeal carcinoma xenograft models as well as for toxicity in NOD scid gamma mice. The Cu(II) complex displayed broad spectrum cytotoxicity against multiple cancer types, including lung, colon, central nervous system, melanoma, ovarian, and prostate cancer cell lines in the NCI-60 panel. The Cu(II) complex did not cause significant induction of cytochrome P450 (CYP) 3A and 1A enzymes but moderately inhibited CYP isoforms 1A2, 2C9, 2C19, 2D6, 2B6, 2C8 and 3A4. The complex significantly inhibited tumor growth in nasopharyngeal carcinoma xenograft bearing mice models at doses which were well tolerated without causing significant or permanent toxic side effects. However, higher doses which resulted in better inhibition of tumor growth also resulted in toxicity.