Chitosan prevents the development of AOM-induced aberrant crypt foci in mice and suppressed the proliferation of AGS cells by inhibiting DNA synthesis.
We study the effect of fungal-derived chitosan on the development of chemical-induced colonic precancerous lesions in ICR mice and delineate its possible molecular mechanisms. In the 2 weeks preventive experiments, mice fed with a diet containing high molecular weight chitosan (HMWC) had significant fewer aberrant crypt foci formation than those fed with control diet. As the treatment extended to 6 weeks, both low molecular weight chitosan (LMWC)- and HMWC-fed mice contained less aberrant crypt foci when compared to control. However, such effect was not observed in mice in the 6 weeks therapeutic experiments. The anti-tumorigenesis effect of water-soluble chitosan oligomer (WSCO) was tested on four cancer cell lines. WSCO significantly suppressed AGS and to a less extent, COLO 205 cells proliferation. Flow cytometry analysis of cell cycle distribution indicated that the percentage of S phase reduced significantly in AGS cells treated with WSCO together with a decrease in DNA synthesis rate in BrdU incorporation assay. WSCO treatment also upregulated cell cycle-related genes p21/Cip and p27/Kip, whereas downregulated that of PCNA.
Lin
Shyr-Yi
SY
Department of Internal Medicine, School of Medicine, Taipei Medical University and Hospital, Taipei, Taiwan.
Chan
Hing-Yuen
HY
Shen
Fung-Hsiu
FH
Chen
Mei-Huei
MH
Wang
Ying-Jan
YJ
Yu
Chung-Keung
CK
D000818:Animals; D001397:Azoxymethane / Q000633:toxicity*; D015153:Blotting, Western; D002273:Carcinogens / Q000633:toxicity; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D004261:DNA Replication / Q000187:drug effects*; D005434:Flow Cytometry; D006801:Humans; D019169:Jurkat Cells; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008970:Molecular Weight; D011230:Precancerous Conditions / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000473:pathology
D002273:Carcinogens; D018797:Cell Cycle Proteins; C400945:water soluble chitin; D048271:Chitosan; D001397:Azoxymethane