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Steroidal Saponins from Paris polyphylla Suppress Adhesion, Migration and Invasion of Human Lung Cancer A549 Cells Via Down-Regulating MMP-2 and MMP-9

  • He, Hao (School of Pharmaceutical Sciences, Xi'an Medical University) ;
  • Zheng, Lei (School of Pharmaceutical Sciences, Xi'an Medical University) ;
  • Sun, Yan-Ping (School of Pharmaceutical Sciences, Xi'an Medical University) ;
  • Zhang, Guang-Wei (Clinical Medicine College, Xi'an Medical University) ;
  • Yue, Zheng-Gang (Shanxi Collaborative Innovation Center of Chinese Medicinal Resource Industrialization, School of Pharmacy, Shanxi College of Traditional Chinese Medicine)
  • Published : 2015.01.22

Abstract

Background: Tumor metastases are the main reasons for oncotherapy failure. Paris polyphylla (Chinese name: Chonglou) has traditionally been used for its anti-cancer actions. In this article, we focus on the regulation of human lung cancer A549 cell metastases and invasion by Paris polyphylla steroidal saponins (PPSS). Materials and Methods: Cell viability was evaluated in A549 cells by MTT assay. Effects of PPSS on invasion and migration were investigated by wound-healing and matrigel invasion chamber assays. Adhesion to type IV collagen and laminin was evaluated by MTT assay. Expression and protease activity of two matrix metalloproteinases (MMPs), MMP-2 and MMP-9, were analyzed by Western blotting and gelatin zymography, respectively. Results: PPSS exerted growth inhibitory effects on A549 cells, and effectively inhibited A549 cell adhesion, migration and invasion in a concentration-dependent manner. Western blotting and gelatin zymography analysis revealed that PPSS inhibited the expression and secretion of MMP-2 and MMP-9 in A549 cells. Conclusions: PPSS has the potential to suppress the migration, adhesion and invasion of A549 cells. PPSS could be a potential candidate for interventions against lung cancer metastases.

References

  1. Al Husaini H, Wheatley-Price P, Clemons M, et al (2009). Prevention and management of bone metastases in lung cancer: a review. J Thorac Oncol, 4, 251-9. https://doi.org/10.1097/JTO.0b013e31819518fc
  2. Cao XL, Xu RJ, Zheng YY, et al (2011). Expression of type IV collagen, metalloproteinase-2, metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in laryngeal squamous cell carcinomas. Asian Pac J Cancer Prev, 12, 3245-9.
  3. Cheng M, Liu L, Yang HS, et al (2014). Circulating tumor cells are associated with bone metastasis of lung cancer. Asian Pac J Cancer Prev, 15, 6369-74. https://doi.org/10.7314/APJCP.2014.15.15.6369
  4. Committee CP (2010). Pharmacopoeia of The People's Republic of China. China Medical Science Press, Beijing.
  5. Friedl P, Wolf K (2003). Tumour-cell invasion and migration: diversity and escape mechanisms. Nat Rev Cancer, 3, 362-74. https://doi.org/10.1038/nrc1075
  6. Guo XT, Wang JF, Zhang LY, et al (2012). Quantitative assessment of the effects of MMP-2 polymorphisms on lung carcinoma risk. Asian Pac J Cancer Prev, 13, 2853-6. https://doi.org/10.7314/APJCP.2012.13.6.2853
  7. Hidalgo M, Eckhardt SG (2001). Development of matrix metalloproteinase inhibitors in cancer therapy. J Natl Cancer Inst, 93, 178-93. https://doi.org/10.1093/jnci/93.3.178
  8. Lee KH (1999). Anticancer drug design based on plant-derived natural products. J Biomed Sci, 6, 236-50.
  9. Li Y, Gu JF, Zou X, et al (2013). The anti-lung cancer activities of steroidal saponins of P. polyphylla Smith var. chinensis (Franch.) Hara through enhanced immunostimulation in experimental Lewis tumor-bearing C57BL/6 mice and induction of apoptosis in the A549 cell line. Molecules, 18, 12916-36. https://doi.org/10.3390/molecules181012916
  10. Li Y, Miao LY, Xiao YL, et al (2014). Elevated platelets enhance cancer cell migration, promote hematogenous metastasis and associate with a poor prognosis in advanced non-small cell lung cancer cases. Asian Pac J Cancer Prev, 15, 139-43. https://doi.org/10.7314/APJCP.2014.15.1.139
  11. Liu MX, Zhou KC, Cao Y (2014). MCRS1 overexpression, which is specifically inhibited by miR-129*, promotes the epithelial-mesenchymal transition and metastasis in non-small cell lung cancer. Mol Cancer, 13, 245. https://doi.org/10.1186/1476-4598-13-245
  12. Newman DJ, Cragg GM (2012). Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Natural Products, 75, 311-35. https://doi.org/10.1021/np200906s
  13. Siegel R, Ma J, Zou Z, et al (2014). Cancer statistics, 2014. CA Cancer J Clin, 64, 9-29. https://doi.org/10.3322/caac.21208
  14. Silvestri GA, Tanoue LT, Margolis ML, et al (2003). The noninvasive staging of non-small cell lung cancer: the guidelines. Chest, 123, 147-56. https://doi.org/10.1378/chest.123.1_suppl.147S
  15. Sone S, Yano S (2007). Molecular pathogenesis and its therapeutic modalities of lung cancer metastasis to bone. Cancer Metastasis Rev, 26, 685-9. https://doi.org/10.1007/s10555-007-9081-z
  16. Wang C, Ma HX, Jin MS, et al (2014). Association of matrix metalloproteinase (MMP)-2 and -9 expression with extra-gastrointestinal stromal tumor metastasis. Asian Pac J Cancer Prev, 15, 4187-92. https://doi.org/10.7314/APJCP.2014.15.10.4187
  17. Wang Y, Zhang YJ, Gao WY, et al (2007). [Anti-tumor constituents from Paris polyphylla var. yunnanensis]. Zhongguo Zhong Yao Za Zhi, 32, 1425-8.
  18. Yadav L, Puri N, Rastogi V, et al (2014). Matrix metalloproteinases and cancer - roles in threat and therapy. Asian Pac J Cancer Prev, 15, 1085-91. https://doi.org/10.7314/APJCP.2014.15.3.1085
  19. Yan LL, Zhang YJ, Gao WY, et al (2009). In vitro and in vivo anticancer activity of steroid saponins of Paris polyphylla var. yunnanensis. Exp Oncol, 31, 27-32.
  20. Yilmaz M, Christofori G, Lehembre F (2007). Distinct mechanisms of tumor invasion and metastasis. Trends Mol Med, 13, 535-41. https://doi.org/10.1016/j.molmed.2007.10.004

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