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

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.