Antitumor effects of various low-molecular-weight chitosans are due to increased natural killer activity of intestinal intraepithelial lymphocytes in sarcoma 180-bearing mice.

Abstract

Various low-molecular-weight chitosans such as the 21-kDa, 46-kDa, and 120-kDa chitosans obtained by enzymatic hydrolysis of a high-molecular-weight chitosan (average molecular weight, 650 kDa) had low viscosity and were water soluble. We examined the antitumor activity of various water-soluble chitosans with different molecular weights in sarcoma 180-bearing mice. A 21-kDa water-soluble chitosan and oligochitosan (100 and 300 mg/kg body) administered by i.g. intubation reduced the tumor growth and final tumor weight in sarcoma 180-bearing mice. A 46-kDa water-soluble chitosan at a dose of 100 mg/kg body reduced the tumor growth and final tumor weight, but had no effect at 300 mg/kg. On the other hand, a 130-kDa water-soluble chitosan had no effect on tumor growth. The 21- and 46-kDa chitosans (10 mg/L) enhanced the natural killer (NK) activity in intestinal intraepithelial lymphocytes (IELs) or splenic lymphocytes. The NK activity of low-molecular-weight chitosan (21- and 46-kDa chitosans)-treated IELs or splenic lymphocytes was stronger than that of high-molecular-weight chitosan (130- and 650-kDa chitosans)-treated IELs or splenic lymphocytes. In addition, low-molecular-weight chitosan-treated IELs or splenic lymphocytes also enhanced the cytotoxic activity against sarcoma 180 cells. In an in vivo study, although low-molecular-weight chitosan-treated IELs had cytotoxic activity against tumor cells, splenic lymphocytes treated with chitosans had no effect. These findings suggest that the antitumor activity of low-molecular-weight chitosans (12- and 46-kDa chitosans) and oligochitosan might be due in part to the enhancement of NK activity in IELs. Thus, the low-molecular-weight chitosans or oligochitosan might be useful in preventing tumor growth through the activation of intestinal immune functions.

• Authors: Yasunori Maeda, Yoshiyuki Kimura
• Journal: The Journal of nutrition (J Nutr) Vol. 134 Issue 4 Pg. 945-50 (Apr 2004) ISSN: 0022-3166 [Print] United States
• PMID: 15051852 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adjuvants, Pharmaceutic
• Antineoplastic Agents
• Water
• Chitin
• Chitosan

Topics

• Adjuvants, Pharmaceutic (therapeutic use)
• Animals
• Antineoplastic Agents (therapeutic use)
• Body Weight
• Chitin (administration & dosage, analogs & derivatives, chemistry, therapeutic use)
• Chitosan
• Erythrocyte Count
• Intestines (immunology)
• Killer Cells, Natural (immunology)
• Leukocyte Count
• Mice
• Molecular Weight
• Organ Size
• Sarcoma 180 (drug therapy, immunology, pathology)
• Solubility
• Water