Abstract |
We previously found that an extracellular polysaccharide, AC-1, produced by Acetobacter polysaccharogenes composed of (1,4)-beta-D-glucan with branches of glucosyl residues showed a strong activity to induce production of interleukin (IL)-12 p40 and tumor necrosis factor-alpha by macrophage cell lines in vitro via Toll-like receptor-4 signaling. In the present study, we examined the effects of oral administration of AC-1 on protection against 2 types of murine B16 melanoma lines, major histocompatibility complex (MHC) class I-negative B16L and MHC class I gene-transfected B16K(b) cells. Mice were inoculated subcutaneously with B16L or B16K(b) cells on day 0 and administrated intragastrically with AC-1 or PBS once every 5 days from 1 day before tumor inoculation. The tumor growth was severely retarded in AC-1-treated mice after subcutaneous inoculation with B16L or B16K(b) cells. The AC-1-treated mice showed augmented natural killer (NK) cell activity against B16L cells, and in vivo depletion of NK cells by antiasialoGM1 antibody (Ab) treatment abrogated the antitumor activity in AC-1-treated mice. On the other hand, AC-1-treated mice inoculated with B16K(b) cells developed a significantly higher level of cytotoxic T-lymphocyte response against B16K(b) cells, and in vivo depletion of CD8(+) T cells by anti-CD8 mAb treatment abrogated the antitumor activity. Thus, AC-1 augmented antitumor activity against different tumors via augmentation of different antitumor mechanisms. These results suggest a possible prophylactic application of AC-1 for human neoplasms irrespective of expression levels of their MHC class I molecules.
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Authors | Yoriyuki Kamiryo, Toshiki Yajima, Kimika Saito, Hitoshi Nishimura, Takashi Fushimi, Yoshifumi Ohshima, Yoshinori Tsukamoto, Seiji Naito, Yasunobu Yoshikai |
Journal | International journal of cancer
(Int J Cancer)
Vol. 115
Issue 5
Pg. 769-76
(Jul 10 2005)
ISSN: 0020-7136 [Print] United States |
PMID | 15729692
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | (c) 2005 Wiley-Liss, Inc. |
Chemical References |
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Topics |
- Acetobacter
(chemistry)
- Administration, Oral
- Animals
- Disease Models, Animal
- Female
- Genes, MHC Class I
- Glucans
(pharmacology)
- HLA Antigens
(biosynthesis)
- Humans
- Killer Cells, Natural
(immunology)
- Male
- Melanoma
(pathology)
- Mice
- Mice, Inbred C57BL
- Skin Neoplasms
(pathology)
- T-Lymphocytes, Cytotoxic
(immunology)
- Tumor Cells, Cultured
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