Chitosan oligosaccharide suppresses tumor progression in a mouse model of colitis-associated colorectal cancer through AMPK activation and suppression of NF-κB and mTOR signaling.
Novel, effective and safe agents are needed for the chemoprevention of colorectal cancer (CRC). This study investigated the effects of chitosan oligosaccharides (COS) on CRC progression and their underlying mechanisms and safety profiles in mice. Using a mouse model of colitis-associated CRC, we found that oral administration of COS (500mg/kg/day) resulted in a ∼60% reduction of tumor size and tumor numbers/sectioning. In addition, COS treatment increased AMPK activity, suppressed the NF-κB-mediated inflammatory response and reduced the expressions of cyclin D1, phosphorylated ribosomal protein S6, and MMP-9 in the colon tissues of these mice. Importantly, administration of COS (500mg/kg/day; 50 days) had no adverse effects on renal or liver functions. Our results indicate that COS suppressed CRC progression via AMPK activation and the suppression of NF-κB and mTOR signaling. COS may be of potential utility in the chemoprevention of CRC.
Department of Physiology, Faculty of Science, Mahidol University, Ratchathewi, Bangkok 10400, Thailand.
Tharinee
T
Mattaveewong
Department of Physiology, Faculty of Science, Mahidol University, Ratchathewi, Bangkok 10400, Thailand.
Preedajit
P
Wongkrasant
Department of Anatomy, Faculty of Science, Mahidol University, Ratchathewi, Bangkok 10400, Thailand.
Sumalee
S
Chanchai
Department of Biochemistry, Faculty of Science, Chulalongkorn University, Phyathai, Bangkok 10330, Thailand.
Rath
R
Pichyangkura
Department of Physiology, Faculty of Science, Mahidol University, Ratchathewi, Bangkok 10400, Thailand; Excellent Center for Drug Discovery (ECDD), Thailand Center of Excellence for Life Sciences (TCELS), Bangkok 10400, Thailand; Center of Excellence on Medical Biotechnology, Ministry of Education, Bangkok 10400, Thailand.
Varanuj
V
Chatsudthipong
Department of Physiology, Faculty of Science, Mahidol University, Ratchathewi, Bangkok 10400, Thailand; Excellent Center for Drug Discovery (ECDD), Thailand Center of Excellence for Life Sciences (TCELS), Bangkok 10400, Thailand; Center of Excellence on Medical Biotechnology, Ministry of Education, Bangkok 10400, Thailand. Electronic address: chatchai.mua@mahidol.ac.th.
Chatchai
C
Muanprasat
D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D048271:Chitosan / Q000737:chemistry*; D003092:Colitis / Q000150:complications / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D019938:Cyclin D1 / Q000378:metabolism; D004195:Disease Models, Animal; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D009844:Oligosaccharides / Q000494:pharmacology* / Q000627:therapeutic use*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects
D016588:Anticarcinogenic Agents; C530105:Ccnd1 protein, mouse; D016328:NF-kappa B; D009844:Oligosaccharides; D019938:Cyclin D1; D048271:Chitosan; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse
AMP-activated protein kinase; Chemoprevention; Chitosan oligosaccharide; Colorectal cancer