A novel strategy for treatment of cancer cachexia targeting xanthine oxidase in the brain

• Published in: Journal of pharmacological sciences Vol. 140; no. 1; pp. 109 - 112
• Main Authors: Uzu, Miaki, Nonaka, Miki, Miyano, Kanako, Sato, Hiromi, Kurebayashi, Nagomi, Yanagihara, Kazuyoshi, Sakurai, Takashi, Hisaka, Akihiro, Uezono, Yasuhito
• Format: Journal Article
• Language: English
• Published: Japan Elsevier B.V 01.05.2019; Elsevier
• Subjects: Administration, Oral; Animals; Brain - enzymology; Brain - metabolism; Cachexia - drug therapy; Cachexia - enzymology; Cachexia - etiology; Cachexia - metabolism; Cancer cachexia; Disease Models, Animal; Febuxostat - administration & dosage; Male; Metabolome; Mice, Inbred BALB C; Neoplasms - complications; Purines - metabolism; Xanthine oxidase; Xanthine Oxidase - metabolism; Xanthine Oxidase - physiology; Metabolome; Xanthine oxidase; Cancer cachexia
• ISSN: 1347-8613; 1347-8648
• DOI: 10.1016/j.jphs.2019.04.005

Cancer cachexia is a systemic wasting syndrome characterized by anorexia and loss of body weight. The xanthine oxidase (XO) inhibitor febuxostat is one of the promising candidates for cancer cachexia treatment. However, cachexic symptoms were not alleviated by oral administration of febuxostat in our cancer cachexia model. Metabolomic analysis with brains of our cachexic model showed that purine metabolism was activated and XO activity was increased, and thus suggested that febuxostat would not reach the brain. Accordingly, targeting XO in the brain, which controls appetite, may be an effective strategy for treatment of cancer cachexia.