title: Carboxyamidotriazole alleviates muscle atrophy in tumor-bearing mice by inhibiting NF-κB and activating SIRT1.
abstract: Cancer cachexia is a complex disorder characterized by inflammatory responses, and it is associated with poor performance status and high mortality rate of cancer patients. Carboxyamidotriazole (CAI), a noncytotoxic chemotherapy agent, shows anti-inflammatory features in the treatment of many diseases. Here, we investigated the preventive and therapeutic effects of CAI on muscle loss that occurred in mice with advanced Lewis lung carcinoma (LLC). The carcass weights of CAI-treated mice were significantly higher than that of mice in the vehicle group from Day 19 to the end of the study. The gastrocnemius and epididymal adipose tissue weights were also increased by CAI treatment. The protective mechanisms might be attributed to the following points: CAI treatment inhibited the proteolysis in muscles by decreasing expressions of muscle-specific FoxO3 transcription factor and ubiquitin E3 ligases (MuRF1 and atrogin1). Moreover, CAI restricted the NF-κB signaling, downregulated the level of TNF-α in muscle and both TNF-α and IL-6 levels in serum, directly stimulated SIRT1 activity in vitro, and increased SIRT1 content in muscle. These results indicate that CAI can alleviate muscle wasting and is a promising drug against lung cancer cachexia.
authors.affiliation: Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Ju
authors.affiliation: Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, China.
authors.forename: De-Chang
authors.initials: DC
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, China.
authors.forename: Cai-Ying
authors.initials: CY
authors.lastname: Ye
authors.affiliation: Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, China. guoleistu@126.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Guo
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000254:growth & development; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002100:Cachexia / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D018827:Carcinoma, Lewis Lung / Q000150:complications / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D009133:Muscular Atrophy / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D056564:Sirtuin 1 / Q000378:metabolism*; D014230:Triazoles / Q000494:pharmacology / Q000627:therapeutic use; D047368:Tumor Burden / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D015850:Interleukin-6; D016328:NF-kappa B; D014230:Triazoles; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse; C062058:carboxyamido-triazole; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1
keywords: CAI; FoxO3; NF-κB; SIRT1; cancer cachexia; muscle wasting