Paris saponin Ⅶ inhibits metastasis by modulating matrix metalloproteinases in colorectal cancer cells

Fan,Lei; Li,Yuhua; Sun,Yang; Yue,Zhenggang; Meng,Jin; Zhang,Xutao; Zhang,Rong; Zhang,Dian; Zhang,Feng; Mei,Qibing

doi:10.3892/mmr.2014.2728

Paris saponin Ⅶ inhibits metastasis by modulating matrix metalloproteinases in colorectal cancer cells

Authors:
- Lei Fan
- Yuhua Li
- Yang Sun
- Zhenggang Yue
- Jin Meng
- Xutao Zhang
- Rong Zhang
- Dian Zhang
- Feng Zhang
- Qibing Mei
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Affiliations: Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Collaborative Innovation Center for Chinese Medicine in Qinba Mountains, Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China, Department of Pharmacy, 309th Hospital of PLA, Beijing 100091, P.R. China
Published online on: October 21, 2014 https://doi.org/10.3892/mmr.2014.2728
Pages: 705-711

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Abstract

Metastasis is the main cause of mortality of patients with cancer‑related disease. Targeting the process of metastasis has been proposed as a potential strategy in cancer treatment. Trillium tschonoskii Maxim., a traditional Chinese medicine, is used for the treatment of numerous diseases, including cancer. The current study aimed to determine the anti‑metastatic effect of Paris saponin VII (PS Ⅶ), which was extracted from T. tschonoskii Maxim., using SW620 and LoVo cells, two human metastatic colorectal cancer (CRC) cell lines. The present study conducted cell attachment, wound healing and migration assays to detect the anti‑metastatic effects of PS VII on colorectal cells. In addition, gelatin zymography assay and western blot analysis were used to detect the possible mechanisms involved. The results of this study demonstrated that PS Ⅶ significantly suppresses the viability, attachment, migration and invasive abilities of CRC cells in a concentration‑dependent manner. In addition, PS Ⅶ reduced the expression levels and activity of matrix metalloproteinase (MMP)‑2 and MMP‑9. These data indicate that PS Ⅶ reduces the metastatic capability of CRC cells, possibly via the downregulation of the expression and activity of MMP‑2 and MMP‑9. These results demonstrate a novel therapeutic potential for PS Ⅶ in anti‑metastatic therapy.

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1	Siegel R, Naishadham D and Jemal A: Cancer statistics, 2012. CA Cancer J Clin. 62:10–29. 2012. View Article : Google Scholar
2	Gupta GP and Massagué J: Cancer metastasis: building a framework. Cell. 127:679–695. 2006. View Article : Google Scholar : PubMed/NCBI
3	Steeg PS: Tumor metastasis: mechanistic insights and clinical challenges. Nat Med. 12:895–904. 2006. View Article : Google Scholar : PubMed/NCBI
4	Sanoff HK, Sargent DJ, Campbell ME, et al: Five-year data and prognostic factor analysis of oxaliplatin and irinotecan combinations for advanced colorectal cancer: N9741. J Clin Oncol. 26:5721–5727. 2008.PubMed/NCBI
5	Prat A, Casado E and Cortés J: New approaches in angiogenic targeting for colorectal cancer. World J Gastroenterol. 13:5857–5866. 2007. View Article : Google Scholar : PubMed/NCBI
6	Sarkar FH, Li Y, Wang Z and Kong D: Cellular signaling perturbation by natural products. Cell Signal. 21:1541–1547. 2009. View Article : Google Scholar : PubMed/NCBI
7	Cragg GM and Newman DJ: Natural products: a continuing source of novel drug leads. Biochim Biophys Acta. 1830:3670–3695. 2013.PubMed/NCBI
8	Reddy L, Odhav B and Bhoola KD: Natural products for cancer prevention: a global perspective. Pharmacol Ther. 99:1–13. 2003. View Article : Google Scholar : PubMed/NCBI
9	Li Q, Xiao M, Guo L, et al: Genetic diversity and genetic structure of an endangered species, Trillium tschonoskii. Biochem Genet. 43:445–458. 2005. View Article : Google Scholar : PubMed/NCBI
10	Yokosuka A and Mimaki Y: Steroidal glycosides from the underground parts of Trillium erectum and their cytotoxic activity. Phytochemistry. 69:2724–2730. 2008. View Article : Google Scholar : PubMed/NCBI
11	Hayes PY, Lehmann R, Penman K, Kitching W and De Voss JJ: Steroidal saponins from the roots of Trillium erectum (Beth root). Phytochemistry. 70:105–113. 2009. View Article : Google Scholar : PubMed/NCBI
12	Ono M, Sugita F, Shigematsu S, et al: Three new steroid glycosides from the underground parts of Trillium kamtschaticum. Chem Pharm Bull (Tokyo). 55:1093–1096. 2007. View Article : Google Scholar : PubMed/NCBI
13	Smicun Y, Gil O, Devine K and Fishman DA: S1P and LPA have an attachment-dependent regulatory effect on invasion of epithelial ovarian cancer cells. Gynecol Oncol. 107:298–309. 2007. View Article : Google Scholar : PubMed/NCBI
14	Gamble JR and Vadas MA: A new assay for the measurement of the attachment of neutrophils and other cell types to endothelial cells. J Immunol Methods. 109:175–184. 1988. View Article : Google Scholar : PubMed/NCBI
15	Hsu SC, Kuo CL, Lin JP, et al: Crude extracts of Euchresta formosana radix inhibit invasion and migration of human hepatocellular carcinoma cells. Anticancer Res. 27:2377–2384. 2007.
16	Huang YT, Hwang JJ, Lee LT, et al: Inhibitory effects of a luteinizing hormone-releasing hormone agonist on basal and epidermal growth factor-induced cell proliferation and metastasis-associated properties in human epidermoid carcinoma A431 cells. Int J Cancer. 99:505–513. 2002. View Article : Google Scholar
17	Surgucheva IG, Sivak JM, Fini ME, Palazzo RE and Surguchov AP: Effect of gamma-synuclein overexpression on matrix metalloproteinases in retinoblastoma Y79 cells. Arch Biochem Biophys. 410:167–176. 2003. View Article : Google Scholar : PubMed/NCBI
18	Qin H, Du X, Zhang Y and Wang R: Platycodin D, a triterpenoid saponin from Platycodon grandiflorum, induces G2/M arrest and apoptosis in human hepatoma HepG2 cells by modulating the PI3K/Akt pathway. Tumour Biol. 35:1267–1274. 2014.PubMed/NCBI
19	Xu MY, Lee DH, Joo EJ, Son KH and Kim YS: Akebia saponin PA induces autophagic and apoptotic cell death in AGS human gastric cancer cells. Food Chem Toxicol. 59:703–708. 2013. View Article : Google Scholar : PubMed/NCBI
20	Yoon JH, Choi YJ and Lee SG: Ginsenoside Rh1 suppresses matrix metalloproteinase-1 expression through inhibition of activator protein-1 and mitogen-activated protein kinase signaling pathway in human hepatocellular carcinoma cells. Eur J Pharmacol. 679:24–33. 2012. View Article : Google Scholar
21	Ha TS, Lee JS, Choi JY and Park HY: Ginseng total saponin modulates podocyte p130Cas in diabetic condition. J Ginseng Res. 37:94–99. 2013. View Article : Google Scholar : PubMed/NCBI
22	Kobayashi H, Mochizuki H, Sugihara K, et al: Characteristics of recurrence and surveillance tools after curative resection for colorectal cancer: a multicenter study. Surgery. 141:67–75. 2007. View Article : Google Scholar
23	Weng CJ and Yen GC: Chemopreventive effects of dietary phytochemicals against cancer invasion and metastasis: phenolic acids, monophenol, polyphenol, and their derivatives. Cancer Treat Rev. 38:76–87. 2012. View Article : Google Scholar
24	Berrier AL and Yamada KM: Cell-matrix adhesion. J Cell Physiol. 213:565–573. 2007. View Article : Google Scholar
25	Friedl P and Wolf K: Tumour-cell invasion and migration: diversity and escape mechanisms. Nat Rev Cancer. 3:362–374. 2003. View Article : Google Scholar : PubMed/NCBI
26	Liska V, Sutnar A, Jr LH, et al: Matrix metalloproteinases and their inhibitors in correlation to proliferative and classical tumour markers during surgical therapy of colorectal liver metastases. Bratisl Lek Listy. 113:108–113. 2012.
27	Langers AM, Verspaget HW, Hawinkels LJ, et al: MMP-2 and MMP-9 in normal mucosa are independently associated with outcome of colorectal cancer patients. Br J Cancer. 106:1495–1498. 2012. View Article : Google Scholar : PubMed/NCBI