title: Quinacrine for extremity melanoma in a mouse model of isolated limb perfusion (ILP).
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA, minhyungkr@gmail.com.
authors.forename: Minhyung
authors.initials: M
authors.lastname: Kim
authors.forename: Asher B
authors.initials: AB
authors.lastname: Blum
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Haslinger
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Donahue
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Fisher
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Skitzki
authors.forename: Il Young
authors.initials: IY
authors.lastname: Park
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents; D004195:Disease Models, Animal; D005121:Extremities; D005260:Female; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D009368:Neoplasm Transplantation; D010477:Perfusion / Q000379:methods*; D011796:Quinacrine / Q000494:pharmacology* / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D016328:NF-kappa B; D016159:Tumor Suppressor Protein p53; D011796:Quinacrine