In vitro and in vivo anticancer effects of Quinoline Platinum(II) complexes in 2D, 3D human osteosarcoma cells and a xenograft tumor in mice.

RESASCO A; CABRERA S; RUIZ M.C; AYALA M; LEON I.E; DI VIRGILIO A.L; ALEMAN J

Simposio; VI Latin American Meeting on Biological Inorganic Chemistry (LABIC); 2018

Platinum-based drugs, mainly cisplatin, are used for the treatment of several kind oftumors such as Osteosarcoma. However, cisplatin treatment often results in the developmentof chemoresistance, leading therapeutic failure [1].Here, the anticancer properties of two different quinoline-platinum complexes([Pt(Cl)2(quinoline)(dmso)] (1) [PtCl(8-O-quinoline)(dmso)] (2) on in vitro (2D and 3D) and invivo models (xenograft tumor of human osteosarcoma in mice) are presented. In this order,compound 2 impaired cell viability to have a more pronounced antitumour effect thancisplatin on MG-63 osteosarcoma cells (IC50 4 μM vs. 39 μM). Besides, compound 2increased ROS production in a dose-manner response and this compound induced early andlate apoptotic fractions of human osteosarcoma cells. Moreover, complex 2 decreased thecell viability of multicellular spheroids and reduced the tumor volume on athymic nude micewithout inducing side effects. Finally, our results indicate that these complexes showed betteranticancer performance than cisplatin on in vitro and in vivo studies. These data showed theimportance of chelation in the antitumor properties, suggesting that the compound 2 might bea promising agent for the treatment of human osteosarcoma tumors resistant to cisplatin.