DOI QR코드

DOI QR Code

Polysaccharide from Polygonatum Inhibits the Proliferation of Prostate Cancer-Associated Fibroblasts Cells

  • Han, Shu-Yu (Institute of Biophysics, Chinese Academy of Sciences) ;
  • Hu, Ming-Hua (Infinitus Chinese Herbal Immunity Research Centre) ;
  • Qi, Guan-Yun (Institute of Biophysics, Chinese Academy of Sciences) ;
  • Ma, Chao-Xiong (Institute of Biophysics, Chinese Academy of Sciences) ;
  • Wang, Yuan-Yuan (Infinitus Chinese Herbal Immunity Research Centre) ;
  • Ma, Fang-Li (Infinitus Chinese Herbal Immunity Research Centre) ;
  • Tao, Ning (Institute of Biophysics, Chinese Academy of Sciences) ;
  • Qin, Zhi-Hai (Institute of Biophysics, Chinese Academy of Sciences)
  • Published : 2016.08.01

Abstract

Inhibition of cancer-associated fibroblasts (CAFs) may improve the efficacy of cancer therapy. Polysaccharide extracted from polygonatum can selectively inhibit the growth of prostate-CAFs (p<0.001) without inhibiting the growth of normal fibroblasts (NAFs). Polysaccharides from polygonatum stimulate autophagy of prostate-CAFs. 3-methyl-adenine(3-MA) is an autophagy inhibitor. 3-MA was added to prostate-CAFs with polysaccharide from polygonatum to determine whether autophagy plays an important role in the restrained effect. Finally, polysaccharide from polygonatum treatment significantly increased the activation of Beclin-1 and LC3, key autophagy proteins. Polysaccharide from polygonatum stimulates autophagy of prostate-CAFs and inhibits prostate-CAF growth, indicating that a novel anti-cancer strategy involves inhibiting the growth of prostate-CAFs.

Keywords

Cancer associated fibroblasts;polysaccharide from polygonatum;autophagy;tumor;therapy

Acknowledgement

Supported by : Nankai University

References

  1. Bastian PJ, Boorjian SA, Bossi A, et al (2012). High-risk prostate cancer: from definetion to contemporary management. Eur Urol, 61, 1096-106. https://doi.org/10.1016/j.eururo.2012.02.031
  2. Chang HY, Chi JT, Dudoit S, et al (2002). Diversity topographic differentiation and positional memory in human fibroblasts. Proc Natl Acad Sci USA, 99, 12877-82. https://doi.org/10.1073/pnas.162488599
  3. Chifenti B, Locci MT, Lazzeri G, et al (2013). Autophagy-related protein LC3 and Beclin-1 in the first trimester of pregnancy. Clin Exp Reprod Med, 40, 33-7. https://doi.org/10.5653/cerm.2013.40.1.33
  4. Duan H, Wang B, Zhang Y (2014). Anti-tumor effects and mechanism of rhizoma polygonatum polysaccharide on H22 tumor bearing mice. Traditional Chinese Drug Res Clin Pharmacol, 25, 5-7.
  5. Erez N, Truitt M, Olson P, et al (2010). Cancer associated fibroblasts are activated in incipient neoplasia to orchestrate tumor-promoting inflammation in an NF-kappa B-dependent manner. Cancer Cell, 17, 135-47. https://doi.org/10.1016/j.ccr.2009.12.041
  6. Ji T, Ding Y, Zhao Y, et al (2015). Peptide assembly integration of fibroblast-targeting and cell-penetration features for enhanced antitumor drug delivery. Adv Mater, 27, 1865-73. https://doi.org/10.1002/adma.201404715
  7. Kalluri R, Zeisberg M (2006). Fibroblasts in cancer. Nat Rev Cancer, 6, 392-401. https://doi.org/10.1038/nrc1877
  8. Liu Z, Ivanoff A, Klominek J (2001). Expression and activity of matrix metalloproteases in human malignant mesothelioma cell lines. Int J Cancer, 91, 638-643. https://doi.org/10.1002/1097-0215(200002)9999:9999<::AID-IJC1102>3.0.CO;2-Y
  9. Pagliarulo V, Bracarda S, Eisenberger MA, et al (2012). Contemporary role of androgen deprivation therapy for prostate cancer. Eur Urol, 61, 11-25. https://doi.org/10.1016/j.eururo.2011.08.026
  10. Parsonage G, Filer AD, Haworth O, et al (2005). A stromal address code defined by fibroblasts. Trends Immunol, 3, 150-6.
  11. San Francisco IF, DeWolf WC, Peehl DM, et al (2004). Expression of transforming growthfactor-beta1 and growth in soft agar differentiate prostate carcinoma-associated fibroblasts from normal prostate fibroblasts. Int J Cancer, 112, 213-8. https://doi.org/10.1002/ijc.20388
  12. Soronen P, Laiti M, Torn S, et al (2004). Sex steroid hormone metabolism and prostate cancer. J Steroid Biochem Mol Biol, 92, 281-6. https://doi.org/10.1016/j.jsbmb.2004.10.004
  13. Stylianopoulos T, Martin JD, Chauhan VP, et al (2012). Causes, consequences, and remedies for growth-induced solid stress in murine and human tumors. Proc Natl Acad Sci USA, 109, 15101-8. https://doi.org/10.1073/pnas.1213353109
  14. Tlsty TD, Coussens LM (2006). Tumor stroma and regulation of cancer development. Annu Rev Pathol, 1, 119-50. https://doi.org/10.1146/annurev.pathol.1.110304.100224
  15. Tomasek JJ, Gabbiani G, Hinz B, et al (2002). Myofibroblasts and mechano regulation of connective tissue remodelling. Nat Rev Mol Cell Biol, 3, 349-63. https://doi.org/10.1038/nrm809
  16. Wang Z, Mary E (2014). Autophagy in kidney health and disease. Choi Antioxidants Redox Signal, 20, 519-38. https://doi.org/10.1089/ars.2013.5363
  17. Wu H, Tao N, Liu X, et al (2012). Polysaccharide from ientinus edodes inhibits the immuneosuppressive function of myeloid-derived suppressor cells. PLoS One, 7, 51751 1-9. https://doi.org/10.1371/journal.pone.0051751
  18. Ying L, Zhao B, Chen K, et al (2012). Progress of research on polygonatum sibiricum. Chinese Wild Plant Resources, 31, 9-13.
  19. Zuhlke KA, Johnson AM, Tomlins SA, et al (2014). Identification of a novel germline SPOP mutation in a family with hereditary prostate cancer. Prostate, 74, 983-90. https://doi.org/10.1002/pros.22818