Inhibitory effects of chitooligosaccharides on tumor growth and metastasis.
Chitooligosaccharides (COS) are hydrolyzed products of chitosan and have been proven to exhibit various biological functions. The objectives of this study were to evaluate the anti-tumor growth, anti-metastatic potency and related pathways of COS extracted from fungi. In in vitro studies, we found that COS significantly inhibited human hepatocellular carcinoma (HepG2) cell proliferation, reduced the percentage of S-phase and decreased DNA synthesis rate in COS-treated HepG2 cells. Expressions of cell cycle-related genes were analyzed and the results indicated that p21 was up-regulated, while PCNA, cyclin A and cdk-2 were down-regulated. Moreover, we also found that the activity of metastatic related protein (MMP-9) could be inhibited by COS in Lewis lung carcinoma (LLC) cells. In in vivo studies, we found that COS inhibited the tumor growth of HepG2 xenografts in severe combined immune deficient (SCID) mice. In a LLC-bearing mouse tumor growth and lung metastasis model, COS inhibited tumor growth and the number of lung colonies in LLC-bearing mice as well as the lung metastasis, and it prolonged the survival time of the LLC-mice. These results suggest a potential anti-tumor growth and anti-metastatic potency of COS in cancer chemoprevention.
Shen
Kun-Te
KT
Department of Environmental and Occupational Health, National Cheng Kung University, Medical College, 138 Sheng-Li Road, Tainan 704, Taiwan.
Chen
Mei-Huei
MH
Chan
Hing-Yuen
HY
Jeng
Jiiang-Huei
JH
Wang
Ying-Jan
YJ
D000818:Animals; D000970:Antineoplastic Agents; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry / Q000494:pharmacology*; D004396:Coloring Agents; D005780:Gelatin / Q000737:chemistry; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D008970:Molecular Weight; D009362:Neoplasm Metastasis / Q000473:pathology / Q000517:prevention & control*; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009844:Oligosaccharides / Q000494:pharmacology*; D013778:Tetrazolium Salts; D013844:Thiazoles
D000970:Antineoplastic Agents; D004396:Coloring Agents; D009844:Oligosaccharides; D013778:Tetrazolium Salts; D013844:Thiazoles; D005780:Gelatin; D048271:Chitosan; D020782:Matrix Metalloproteinases; C022616:thiazolyl blue