Chitooligosaccharides and N-acetyl-D-glucosamine stimulate peripheral blood mononuclear cell-mediated antitumor immune responses

Xu,Wenhua; Jiang,Changqing; Kong,Xiaoying; Liang,Ye; Rong,Mi; Liu,Wanshun

doi:10.3892/mmr.2012.918

Chitooligosaccharides and N-acetyl-D-glucosamine stimulate peripheral blood mononuclear cell-mediated antitumor immune responses

Authors:
- Wenhua Xu
- Changqing Jiang
- Xiaoying Kong
- Ye Liang
- Mi Rong
- Wanshun Liu
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Affiliations: College of Marine Life Sciences, Ocean University of China, Qingdao, Shandong, P.R. China, Department of Pathology, Municipal Hospital of Qingdao, Qingdao, Shandong, P.R. China
Published online on: May 16, 2012 https://doi.org/10.3892/mmr.2012.918
Pages: 385-390

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Abstract

The aim of the present study was to evaluate the anticancer effects of chitooligosaccharides (COS) and N-acetyl-D-glucosamine (NAG), as well as to investigate the possible mechanisms involved. MTT assay and flow cytometry were used to evaluate the effect of various concentrations of COS and NAG on the proliferation and differentiation of peripheral blood mononuclear cells (PBMCs). In addition, sarcoma 180 cells were transplanted into mice to establish a tumor model. COS and NAG were administered by gavage of various doses. The tumor inhibition rate, thymus and spleen indexes, natural killer (NK) cell activity, and interleukin-2 (IL-2) and interferon-γ (IFN-γ) serum levels were detected. Vascular endothelial growth factor (VEGF) expression levels, an important marker of angiogenesis, were also detected. As shown by immunohistochemistry, VEGF mRNA expression was decreased following treatment with COS and NAG, indicating that COS and NAG have an inhibitory effect on the expression of VEGF. The results from this study indicate that COS administered at a dose of 100 mg/kg and NAG at a dose of 300 mg/kg or 500 mg/kg can not only promote the differentiation of PBMCs and the secretion of IL-2 and IFN-γ, but can also inhibit the expression of VEGF mRNA in sarcoma 180 tumors. Our results show that the antitumor and immunoregulatory effects of COS and NAG are dose-dependent. Furthermore, the antitumor effect is achieved by the improvement of immunoregulation indirectly.

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1	Billiau A: Interferon-γ: biology and role in pathogenesis. Advances Immunol. 62:61–130. 1996.
2	Han YP, Zhao LH and Wu HM: Mechanism of ol igochitosan-induced macrophage activation. Zhejiang Da Xue Xue Bao Yi Xue Ban. 35:265–272. 2006.(In Chinese).
3	Ko S, Takeshi M, Yoshio O, Akio T, Shigeo S and Masuko S: Antitumor effect of hexa-N-acetylchitohexaose and chitohexaose. Carbohydr Res. 151:403–408. 1986. View Article : Google Scholar
4	Muzzarelli RAA: Chitin. Oxford Pergamon Press; London: pp. 262–270. 1977
5	Qin CQ, Du YM, Xiao L and Li Z: Enzymic preparation of water-soluble chitosan and their antitumor activity. Int J Biol Macromol. 31:111–117. 2002. View Article : Google Scholar : PubMed/NCBI
6	Hanahan D and Folkman J: Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell. 86:353–364. 1996. View Article : Google Scholar : PubMed/NCBI
7	Xiao BG, Ma CG, Xu LY, Hans L and Lu CZ: IL-12/IFN-γ/NO axis plays critical role in development of Th1-mediated experimental autoimmune encephalomyelitis. Mol Immnol. 45:1191–1196. 2008.
8	Caroline B, Derek D, Fran B and Frances B: Involvement of both intrinsic and extrinsic pathways in IFN-γ-induced apoptosis that are enhanced with cisplatin. Eur J Cancer. 41:1474–1486. 2005.
9	Tsiavou A, Hatziagelaki E, Chaidaroglou A, Koniavitou K, Degiannis D and Raptis SA: Correlation between intracellular interferon-γ ( IFN-γ) production by CD4⁺ and CD8⁺ lymphocytes and IFN-γ gene polymorphism in patients with type 2 diabetes mellitus and latent autoimmune diabetes of adults (LADA). Cytokine. 31:135–141. 2005.
10	Wang XB, Liu QH, Wang P, Tang W and Hao Q: Study of cell killing effect on S180 by ultrasound activating protoporphyrin IX. Ultrasonics. 48:135–140. 2008. View Article : Google Scholar : PubMed/NCBI
11	Cao L, Liu XZ, Qian TX, et al: Antitumor and immunomodulatory activity of arabinoxylans: a major constituent of wheat bran. Int J Biol Macromol. 48:160–164. 2011. View Article : Google Scholar : PubMed/NCBI
12	Nie XH, Shi BJ, Ding YT and Tao WY: Antitumor and immunomodulatory effects Weikangfu granule compound in tumor-bearing mice. Curr Ther Res. 67:138–150. 2006. View Article : Google Scholar : PubMed/NCBI
13	Lee JK, Lim HS and Kim JH: Cytotoxic activity of aminoderivatized cationic chitosan derivatives. Bioorg Med Chem Lett. 12:2949–2951. 2002. View Article : Google Scholar : PubMed/NCBI
14	Pae HO, Seo WG, Kim NY, et al: Induction of granulocytic differentiation in acute promyelocytic leukemia cells (HL-60) by watersoluble chitosan oligomer. Leuk Res. 25:339–346. 2001. View Article : Google Scholar : PubMed/NCBI
15	Prashanth KVH and Tharanathan RN: Depolymerized products of chitosan as potent inhibitors of tumor-induced angiogenesis. Biochim Biophys Acta. 1722:22–29. 2005. View Article : Google Scholar : PubMed/NCBI
16	Huang RH, Mendis E, Rajapakse N and Kim SK: Strong electronic charge as an important factor for anticancer activity of chitooligosaccharides (COS). Life Sci. 78:2399–2408. 2006. View Article : Google Scholar : PubMed/NCBI
17	Cao XM, Xu HJ, Shang M and Liu WS: Experimental study on antitumor activities and immunity regulation of chitooligosaccharide. J Harbin Univ Commerce (Natural Sciences Edition). 22:8–10. 2006.
18	He H, Zhang H, Li B, et al: Blockade of the sonic hedgehog signalling pathway inhibits choroidal neovascularization in a laser-induced rat model. J Huazhong Univ Sci Technolog Med Sci. 30:659–665. 2010. View Article : Google Scholar : PubMed/NCBI
19	Huang Y, Hua K, Zhou X, et al: Activation of the PI3K/AKT pathway mediates FSH-stimulated VEGF expression in ovarian serous cystadenocarcinoma. Cell Res. 18:780–791. 2008. View Article : Google Scholar : PubMed/NCBI
20	Maeda Y and Kimura Y: Antitumor effects of various low-molecular weight chitosans are due to increased natural killer activity of intestinal intraepithelial lymphocytes in sarcoma 180-bearing mice. J Nutr. 134:945–950. 2004.
21	Lindholm CK: IL-2 receptor signaling through the Shb adaptor protein in T and NK cells. Biochem Biophys Res Commun. 296:929–936. 2002. View Article : Google Scholar : PubMed/NCBI
22	Ma A, Koka R and Burkett P: Diverse functions of IL-2, IL-15, and IL-7 in lymphoid homeostasis. Ann Rev Immunol. 24:657–679. 2006. View Article : Google Scholar : PubMed/NCBI
23	Choi JM, Kim HJ, Lee KY, Choi HJ, Lee IS and Kang BY: Increased IL-2 production in T cells by xanthohumol through enhanced NF-AT and AP-1 activity. Int Immunopharmacol. 9:103–107. 2009. View Article : Google Scholar : PubMed/NCBI
24	Yong HA and Hardy KJ: Role of interferon-gamma in immune cell regulation. J Leukoc Biol. 58:373–378. 1995.
25	Sandra G and Filippo B: IFN-γ Expression in macrophages and its possible biological significance. Cytokine Growth Factor Rev. 9:117–123. 1998.
26	Xu QS, Bai XF and Du YG: Progress on anti-tumor activity of oligochitosan and its derivates. Food and Drug. 10:60–62. 2008.