Oral administration of xanthan gum enhances antitumor activity through Toll-like receptor 4.
OBJECTIVE
Xanthan gum (XG) is a complex exopolysaccharide produced by the plant-pathogenic bacterium Xanthomonas campestris pv. and is widely used as a thickener or viscosifier. We examined in this study the antitumor effects of XG.


METHODS
Cytokine production by XG-stimulated murine macrophage cell lines, J772 and RAW264.7, and peritoneal adherent cells from wild type C57BL/6 mice, TLR2 or MyD88-deficient mice, C3H/HeN, and TLR4-mutant C3H/HeJ mice were examined. In order to examine in vivo antitumor effects of XG, mice were inoculated subcutaneously with tumor cells and administered orally with XG once every 5days from 1day before the tumor inoculation. Tumor growth, mouse survival, NK activity, and tumor-specific cytotoxicity were examined.


RESULTS
In vitro culture with XG induced interleukin-12 and tumor necrosis factor-alpha production from macrophages. XG stimulated macrophages in a MyD88-dependent manner and was mainly recognized by Toll-like receptor 4 (TLR4). Oral administration of XG significantly retarded tumor growth and prolonged survival of the mice inoculated subcutaneously with B16K(b) melanoma cells. NK activity as well as tumor-specific cytotoxicity of CD8 T cells was augmented in the XG-treated mice. The in vivo antitumor effects of XG were also dependent on TLR-4, as C3H/HeJ mice, which lack TLR4 signaling, exhibited no effect of XG on the growth of syngeneic bladder tumor, MBT-2.


CONCLUSIONS
These results suggest beneficial effects of oral administration of XG on immune-surveillance against neoplasms.
Division of Host Defense, Research Center for Prevention of Infectious Disease, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
Ario
A
Takeuchi
Yoriyuki
Y
Kamiryou
Hisakata
H
Yamada
Masatoshi
M
Eto
Kensuke
K
Shibata
Kennichi
K
Haruna
Seiji
S
Naito
Yasunobu
Y
Yoshikai
D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D048708:Cell Growth Processes / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000235:genetics; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics; D009368:Neoplasm Transplantation; D011135:Polysaccharides, Bacterial / Q000008:administration & dosage*; D051195:Toll-Like Receptor 2 / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
D000970:Antineoplastic Agents; D053594:Myeloid Differentiation Factor 88; D011135:Polysaccharides, Bacterial; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; C002563:xanthan gum