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Quinacrine for extremity melanoma in a mouse model of isolated limb perfusion (ILP).

Research paper by Minhyung M Kim, Asher B AB Blum, Michelle L ML Haslinger, Michael J MJ Donahue, Daniel T DT Fisher, Joseph J JJ Skitzki, Il Young IY Park

Indexed on: 08 Jul '14Published on: 08 Jul '14Published in: Surgery Today



Abstract

Quinacrine is a relatively non-toxic drug, once given almost exclusively for malaria. However, recent studies show that quinacrine can suppress nuclear factor-κB (NF-κB), and activate p53 signaling. We investigated the anti-cancer effect of quinacrine, using a novel mouse model of isolated limb perfusion (ILP) for extremity melanoma.Female C57BL/6 mice (22-25 g) were injected with B16 melanoma cells (1 × 10(5)) subcutaneously in the distal thigh. After 7 days of tumor establishment, mice were perfused with either PBS, melphalan (90 µg), or quinacrine (3.5 and 4.5 mg) through the superficial femoral artery for 30 min at either 37 or 42 °C in a non-oxygenated circuit. We analyzed morbidity, toxicity, tumor apoptosis, and responses.Melanoma cell death following in vitro exposure to quinacrine was dose and time dependent. A significant decrease in mean tumor volume was observed after perfusion with low-dose and high-dose quinacrine (both P = 0.002) at 37 °C as well as after perfusion with low-dose quinacrine (P = 0.0008) at 42 °C.Quinacrine has demonstrable efficacy against melanoma cells in vitro and in a clinically relevant model of ILP. Further studies to evaluate the optimal conditions for quinacrine usage are warranted.