Astragalus Polysaccharide Mediates Immunomodulatory Effects on Crosstalk between Human Peripheral Blood Mononuclear Cells and Ovarian Cancer Cell Line
Abstract
Astragalus polysaccharide (APS) is a functional component of Astragalus membranaceus with antitumor and immunomodulatory properties. This study evaluated the effect of APS on the peripheral blood mononuclear cell (PBMC) proliferation, cytokine secretion, and regulatory T cell (Treg) induction in an in vitro coculture model of human PBMCs and A2780 human ovarian cancer cells.
PBMC proliferation and Treg frequency were measured by flow cytometry. Cytokine levels were assessed by enzyme-linked immunosorbent assay.
APS significantly enhanced the PBMC proliferation, reduced Treg frequency, decreased anti-inflammatory cytokines including interleukin [IL]-10, transforming growth factor beta (TGF-β), and vascular endothelial growth factor-A (VEGF-A), and increased the pro-inflammatory cytokine IL-6.
These findings suggest that APS may be an effective immunomodulatory supplement for cancer therapy, particularly for ovarian cancer by enhancing antitumor immune responses.
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26. Holmgaard RB, Zamarin D, Li Y, Gasmi B, Munn DH, Allison JP, et al. Tumor-expressed IDO recruits and activates MDSCs in a Treg-dependent manner. Cell reports. 2015;13(2):412-24.
27. Feyler S, Scott GB, Parrish C, Jarmin S, Evans P, Short M, et al. Tumour cell generation of inducible regulatory T-cells in multiple myeloma is contact-dependent and antigen-presenting cell-independent. PloS one. 2012;7(5):e35981.
28. Du X, Zhao B, Li J, Cao X, Diao M, Feng H, et al. Astragalus polysaccharides enhance immune responses of HBV DNA vaccination via promoting the dendritic cell maturation and suppressing Treg frequency in mice. Int Immunopharmacol. 2012;14(4):463-70.
29. Hoeppli RE, Wu D, Cook L, Levings MK. The environment of regulatory T cell biology: cytokines, metabolites, and the microbiome. Front Immunol. 2015;6:61.
30.Tian Q-E, Yan M, Cai H-L, Tan Q-Y, Zhang W-Y. Astragalus polysaccharides can regulate cytokine and P-glycoprotein expression in H22 tumor-bearing mice. World J Gastroenterol. 2012;18(47):7079.
31. Kong F, Chen T, Li X, Jia Y. The Current Application and Future Prospects of Astragalus Polysaccharide Combined With Cancer Immunotherapy: A Review. Front Pharmacol. 2021;12:737674.
32. Du X, Chen X, Zhao B, Lv Y, Zhang H, Liu H, et al. Astragalus polysaccharides enhance the humoral and cellular immune responses of hepatitis B surface antigen vaccination through inhibiting the expression of transforming growth factor β and the frequency of regulatory T cells. FEMS Immunol Med Microbiol. 2011;63(2):228-35.
33. Horikawa N, Abiko K, Matsumura N, Hamanishi J, Baba T, Yamaguchi K, et al. Expression of Vascular Endothelial Growth Factor in Ovarian Cancer Inhibits Tumor Immunity through the Accumulation of Myeloid-Derived Suppressor CellsVEGF Induces MDSCs and Blocks Tumor Immunity in HGSOC. Clin Cancer Res. 2017;23(2):587-99.
34. Zhao L, Zhong Y, Liang J, Gao H, Tang N. Effect of Astragalus polysaccharide on the expression of VEGF and EGFR in mice with Lewis transplantable lung cancer. J Coll Physicians Surg Pak. 2019;29(4):392-4.
2. Yin S-Y, Wei W-C, Jian F-Y, Yang N-S. Therapeutic applications of herbal medicines for cancer patients. Evid Based Complement Alternat Med. 2013;2013.
3. Jantan I, Ahmad W, Bukhari SNA. Plant-derived immunomodulators: an insight on their preclinical evaluation and clinical trials. Front Plant Sci. 2015;6:655.
4. Auyeung KK, Han Q-B, Ko JK. Astragalus membranaceus: a review of its protection against inflammation and gastrointestinal cancers. Am J Chin Med. 2016;44(01):1-22.
5. Liu P, Zhao H, Luo Y. Anti-aging implications of Astragalus membranaceus (Huangqi): a well-known Chinese tonic. Aging Dis. 2017;8(6):868.
6. Chen Z, Liu L, Gao C, Chen W, Vong CT, Yao P, et al. Astragali Radix (Huangqi): A promising edible immunomodulatory herbal medicine. J Ethnopharmacol. 2020;258:112895.
7. Yang B, Xiao B, Sun T. Antitumor and immunomodulatory activity of Astragalus membranaceus polysaccharides in H22 tumor-bearing mice. Int J Biol Macromol. 2013;62:287-90.
8. Zheng Y, Ren W, Zhang L, Zhang Y, Liu D, Liu Y. A review of the pharmacological action of Astragalus polysaccharide. Front Pharmacol. 2020;11:349.
9. Li ZX, Zhao GD, Xiong W, Linghu KG, Ma QS, Cheang WS, et al. Immunomodulatory effects of a new whole ingredients extract from Astragalus: a combined evaluation on chemistry and pharmacology. Chinese Med. 2019;14(1):1-10.
10. Wang J, Jia J, Song L, Gong X, Xu J, Yang M, et al. Extraction, structure, and pharmacological activities of Astragalus polysaccharides. Applied Sci. 2018;9(1):122.
11. Yu J, Ji H-y, Liu A-j. Alcohol-soluble polysaccharide from Astragalus membranaceus: Preparation, characteristics and antitumor activity. Int J Biol Macromol. 2018;118:2057-64.
12. Chen F, Huang G. Preparation and immunological activity of polysaccharides and their derivatives. Int J Biol Macromol. 2018;112:211-6.
13. Zhou L, Liu Z, Wang Z, Yu S, Long T, Zhou X, et al. Astragalus polysaccharides exerts immunomodulatory effects via TLR4-mediated MyD88-dependent signaling pathway in vitro and in vivo. Sci Rep. 2017;7(1):1-13.
14. Zhang P, Wang J, Wang W, Liu X, Liu H, Li X, et al. Astragalus polysaccharides enhance the immune response to avian infectious bronchitis virus vaccination in chickens. Microbial pathogenesis. 2017;111:81-5.
15. Sheik A, Kim K, Varaprasad GL, Lee H, Kim S, Kim E, et al. The anti-cancerous activity of adaptogenic herb Astragalus membranaceus. Phytomedicine. 2021;91:153698.
16. Guo Y, Zhang Z, Wang Z, Liu G, Liu Y, Wang H. Astragalus polysaccharides inhibit ovarian cancer cell growth via microRNA-27a/FBXW7 signaling pathway. Biosci Rep. 2020;40(3).
17. Chen L, He C, Zhou M, Long J, Li L. Research Progress on the Mechanisms of Polysaccharides against Gastric Cancer. Molecules. 2022;27(18):5828.
18. Yang S, Sun S, Xu W, Yu B, Wang G, Wang H. Astragalus polysaccharide inhibits breast cancer cell migration and invasion by regulating epithelial‑mesenchymal transition via the Wnt/β‑catenin signaling pathway. Mol Med Rep. 2020;21(4):1819-32.
19. Chu Y, Fang Y, Chi J, Li J, Zhang D, Zou Y, et al. Astragalus polysaccharides decrease proliferation, migration, and invasion but increase apoptosis of human osteosarcoma cells by up-regulation of microRNA-133a. Braz J Med Biol Res. 2018;51(12):e7665.
20. Li W, Hu X, Wang S, Jiao Z, Sun T, Liu T, et al. Characterization and antitumor bioactivity of astragalus polysaccharides by immunomodulation. Int J Biol Macromol. 2020;145:985-97.
21. Liu Q-y, Yao Y-m, Zhang S-w, Sheng Z-y. Astragalus polysaccharides regulate T cell-mediated immunity via CD11chighCD45RBlow DCs in vitro. J Ethnopharmacol. 2011;136(3):457-64.
22. Lim SM, Park HB, Jin JO. Polysaccharide from Astragalus membranaceus promotes the activation of human peripheral blood and mouse spleen dendritic cells. Chin J Nat Med. 2021;19(1):56-62.
23. Barnes TC, Anderson ME, Moots RJ. The Many Faces of Interleukin-6: The Role of IL-6 in Inflammation, Vasculopathy, and Fibrosis in Systemic Sclerosis. Int J Rheumatol. 2011;2011:721608.
24. Akira S, Hirano T, Taga T, Kishimoto T. Biology of multifunctional cytokines: IL 6 and related molecules (IL 1 and TNF). FASEB J. 1990;4(11):2860-7.
25. Nowak M, Klink M, Glowacka E, Sulowska Z, Kulig A, Szpakowski M, et al. Production of cytokines during interaction of peripheral blood mononuclear cells with autologous ovarian cancer cells or benign ovarian tumour cells. Scand J Immunol. 2010;71(2):91-8.
26. Holmgaard RB, Zamarin D, Li Y, Gasmi B, Munn DH, Allison JP, et al. Tumor-expressed IDO recruits and activates MDSCs in a Treg-dependent manner. Cell reports. 2015;13(2):412-24.
27. Feyler S, Scott GB, Parrish C, Jarmin S, Evans P, Short M, et al. Tumour cell generation of inducible regulatory T-cells in multiple myeloma is contact-dependent and antigen-presenting cell-independent. PloS one. 2012;7(5):e35981.
28. Du X, Zhao B, Li J, Cao X, Diao M, Feng H, et al. Astragalus polysaccharides enhance immune responses of HBV DNA vaccination via promoting the dendritic cell maturation and suppressing Treg frequency in mice. Int Immunopharmacol. 2012;14(4):463-70.
29. Hoeppli RE, Wu D, Cook L, Levings MK. The environment of regulatory T cell biology: cytokines, metabolites, and the microbiome. Front Immunol. 2015;6:61.
30.Tian Q-E, Yan M, Cai H-L, Tan Q-Y, Zhang W-Y. Astragalus polysaccharides can regulate cytokine and P-glycoprotein expression in H22 tumor-bearing mice. World J Gastroenterol. 2012;18(47):7079.
31. Kong F, Chen T, Li X, Jia Y. The Current Application and Future Prospects of Astragalus Polysaccharide Combined With Cancer Immunotherapy: A Review. Front Pharmacol. 2021;12:737674.
32. Du X, Chen X, Zhao B, Lv Y, Zhang H, Liu H, et al. Astragalus polysaccharides enhance the humoral and cellular immune responses of hepatitis B surface antigen vaccination through inhibiting the expression of transforming growth factor β and the frequency of regulatory T cells. FEMS Immunol Med Microbiol. 2011;63(2):228-35.
33. Horikawa N, Abiko K, Matsumura N, Hamanishi J, Baba T, Yamaguchi K, et al. Expression of Vascular Endothelial Growth Factor in Ovarian Cancer Inhibits Tumor Immunity through the Accumulation of Myeloid-Derived Suppressor CellsVEGF Induces MDSCs and Blocks Tumor Immunity in HGSOC. Clin Cancer Res. 2017;23(2):587-99.
34. Zhao L, Zhong Y, Liang J, Gao H, Tang N. Effect of Astragalus polysaccharide on the expression of VEGF and EGFR in mice with Lewis transplantable lung cancer. J Coll Physicians Surg Pak. 2019;29(4):392-4.
| Files | ||
| Issue | Vol 22 No 2 (2023) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijaai.v22i2.12678 | |
| Keywords | ||
| Astragalus polysaccharides Inflammatory cytokines Ovarian cancer Regulatory T cells Tumor microenvironment | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Shokati E, Motallebnezhad M, Safari E. Astragalus Polysaccharide Mediates Immunomodulatory Effects on Crosstalk between Human Peripheral Blood Mononuclear Cells and Ovarian Cancer Cell Line. Iran J Allergy Asthma Immunol. 2023;22(2):172-182.
