CQ is an old drug that was commonly used to treat fungal/protozoal infections of the gastrointestinal tract. Patients in Japan taking it developed subacute myelo-optic neuropathy which resulted in CQ being discontinued for oral use. Recently, extensive research has been done in regards to CQ’s use for cancer treatment.
Dr. Q. Ping Dou and his team at the Karmanos Cancer Institute reviewed recent research literature and patents involving CQ for cancer therapy. They found that CQ had exhibited anti-tumor activities in a variety of cancer cell lines in preclinical studies. CQ inhibited the growth of cancer cells and was cytotoxic to cancer cells. However, its positive preclinical results did not translate to clinical efficacy. Results of a clinical trial showed that CQ had low therapeutic efficacy, which was probably due to CQ not effectively being absorbed by tumor cells in vivo.
In this review article, Dou’s team also summarized recent findings on several CQ analogues, novel combinations of CQ with other drugs, and novel metal complexes containing CQ; all these preclinical approaches demonstrate strong anti-cancer activities. Promising examples include a gellan gum/glucosamine/CQ film that could be used for treating oral and skin cancers; the CQ analogue nitroxoline, as an anti-cancer agent demonstrated higher potency and lower neurotoxicity than CQ; combining CQ with docahexaenoic acid or disulfiram showed synergistic cytotoxicity; CQ when complexed with ruthenium or oxovanadium (IV) potently inhibited cancer cell growth. The authors of this review article also summarized applications of CQ-related patents for cancer therapy.
The first author of the review article, Raheel Khan, concluded, “Because of the poor clinical results in patients, future efforts should be focused on discovering and researching different combinations, delivery methods, and analogues of clioquinol for use in cancer therapy. The research summarized in our review article can help guide future cancer research to take advantage of the insights gained from preclinical studies on clioquinol”.
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Keywords: Cancer, clioquinol, copper ionophore, cytotoxicity, proteasome, zinc ionophore.
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