Selaginella tamariscina extract suppresses TPA-induced invasion and metastasis through inhibition of MMP-9 in human nasopharyngeal carcinoma HONE-1 cells

BMC Complementary and Alternative Medicine

Chiao-Wen Lin⁷  Mu-Kuan Chen³  Huang-Pin Lin⁴  Hsin-Yu Ho⁶  Yi-Hsien Hsieh¹  Shun-Fa Yang⁵  Chun-Yi Chuang⁴  Buor-Chang Wu²  Chung-Han Hsin⁴ 

[1] Department of Biochemistry, School of Medicine, Chung Shan Medical University, Taichung, Taiwan;Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan;Department of Otorhinolaryngology-Head and Neck Surgery, Changhua Christian Hospital, Changhua, Taiwan;Department of Otolaryngology, Chung Shan Medical University Hospital, Taichung, Taiwan;Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan;Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan;Institute of Oral Sciences, Chung Shan Medical University, 110 Chien-Kuo N. Road, Section 1, Taichung, Taiwan

关键词: Nasopharyngeal carcinoma;    Invasion;    MMP-9;    Selaginella tamariscina;   

Others  :  1220986
DOI  :  10.1186/1472-6882-13-234

 received in 2013-05-15, accepted in 2013-09-19,  发布年份 2013

【 摘 要 】

Background

Nasopharyngeal carcinoma (NPC) is known for its high incidence of neck lymph node metastasis, which represents poor prognosis. The present study aimed to examine the anti-metastatic properties of Selaginella tamariscina extract (STE) in human nasopharyngeal carcinoma HONE-1 cells in vitro.

Methods

Cell viability was examined by MTT assay, whereas cell motility was measured by invasive, migration and would healing assays. Real-time PCR, and promoter assays confirmed the inhibitory effects of STE on matrix metalloproteinase-9 (MMP-9) mRNA level in HONE-1 cells.

Results

The STE inhibits 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced HONE-1 cell migration and invasion in a concentration-dependent manner. By zymographic and Western blot analyses, STE was shown to inhibit the activities and expression of MMP-9. Treatment of STE on TPA-induced HONE-1 cells inhibited MMP-9 expression and ERK1/2 phosphorylation without affecting JNK and p38 phosphorylation.

Conclusions

STE inhibits MMP-9 expression and HONE-1 cell metastasis. Its inhibitory effects may involve the Src/FAK/ERK 1/2 pathway. STE may have the potential of being an anti-metastatic agent against NPC.

【 授权许可】

   
2013 Hsin et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Wei WI, Sham JS: Nasopharyngeal carcinoma. Lancet 2005, 365:2041-2054.
• [2]Chua DT, Sham JS, Wei WI, Ho WK, Au GK: The predictive value of the 1997 American joint committee on cancer stage classification in determining failure patterns in nasopharyngeal carcinoma. Cancer 2001, 92:2845-2855.
• [3]Chan KY, Yen LK, Chu NM, Tan TD, Tsou MH, Huang AT: Prognostic features and treatment outcome in locoregionally advanced nasopharyngeal carcinoma following concurrent chemotherapy and radiotherapy. Int J Radiat Oncol Biol Phys 1998, 41:755-762.
• [4]Hoon DS, Ferris R, Tanaka R, Chong KK, Alix-Panabieres C, Pantel K: Molecular mechanisms of metastasis. J Surg Oncol 2011, 103:508-517.
• [5]Westermarck J, Kahari VM: Regulation of matrix metalloproteinase expression in tumor invasion. FASEB J 1999, 13:781-792.
• [6]Yoon SO, Park SJ, Yun CH, Chung AS: Roles of matrix metalloproteinases in tumor metastasis and angiogenesis. J Biochem Mol Biol 2003, 36:128-137.
• [7]Bjorklund M, Koivunen E: Gelatinase-mediated migration and invasion of cancer cells. Biochim Biophys Acta 2005, 1755:37-69.
• [8]Yang SF, Hsieh YS, Lin CL, Hsu NY, Chiou HL, Chou FP, Chu SC: Increased plasma levels of urokinase plasminogen activator and matrix metalloproteinase-9 in nonsmall cell lung cancer patients. Clin Chim Acta 2005, 354:91-99.
• [9]Cheong H, Ryu SY, Oak MH, Cheon SH, Yoo GS, Kim KM: Studies of structure activity relationship of flavonoids for the anti-allergic actions. Arch Pharm Res 1998, 21:478-480.
• [10]Zheng HZ, Dong ZH, She J: Modern Study of Traditional Chinese Medicine. Beijing: Xue Yuan Press; 1998:3033-3036.
• [11]Shimada Y, Konishi T, Kiyosawa S: Studies on oligosaccharides of plants in the selaginellaacea in Japan. Shoyakugaku Zasshi 1984, 38:207-211.
• [12]Miao N, Tao H, Tong C, Xuan H, Zhamg G: The Selaginella tamariscina (Beauv.) spring complex in the treatment of experimental diabetes and its effect on blood rheology. Zhongguo Zhong Yao Za Zhi 1996, 21:493-495.
• [13]Zheng XK, Zhang L, Wang WW, Wu YY, Zhang QB, Feng WS: Anti-diabetic activity and potential mechanism of total flavonoids of Selaginella tamariscina (Beauv.) Spring in rats induced by high fat diet and low dose STZ. J Ethnopharmacol 2011, 137:662-668.
• [14]Lee IS, Nishikawa A, Furukawa F, Kasahara K, Kim SU: Effects of Selaginella tamariscina on in vitro tumor cell growth, p53 expression. G1 arrest and in vivo gastric cell proliferation. Cancer Lett 1999, 144:93-99.
• [15]Yang SF, Chu SC, Liu SJ, Chen YC, Chang YZ, Hsieh YS: Antimetastatic activities of Selaginella tamariscina (Beauv.) on lung cancer cells in vitro and in vivo. J Ethnopharmacol 2007, 110:483-489.
• [16]Kuo YC, Sun CM, Tsai WJ, Ou JC, Chen WP, Lin CY: Chinese herbs as modulators of human mesangial cell proliferation: preliminary studies. The J Lab Clin Med 1998, 132:76-85.
• [17]Chang YZ, Yang MW, Wang GJ: A new mass spectrometry electrospray tip obtained via precise mechanical micromachining. Anal Bioanal Chem 2005, 383:76-82.
• [18]Wei CW, Lin CC, Yu YL, Lin CY, Lin PC, Wu MT, Chen CJ, Chang W, Lin SZ, Chen YL, Harn HJ: n-Butylidenephthalide induced apoptosis in the A549 human lung adenocarcinoma cell line by coupled down-regulation of AP-2alpha and telomerase activity. Acta Pharmacol Sin 2009, 30:1297-1306.
• [19]Chu SC, Chiou HL, Chen PN, Yang SF, Hsieh YS: Silibinin inhibits the invasion of human lung cancer cells via decreased productions of urokinase-plasminogen activator and matrix metalloproteinase-2. Mol Carcinog 2004, 40:143-149.
• [20]Yang SF, Chu SC, Chiang IC, Kuo WF, Chiou HL, Chou FP, Kuo WH, Hsieh YS: Excessive matrix metalloproteinase-9 in the plasma of community-acquired pneumonia. Clin Chim Acta 2005, 352:209-215.
• [21]Yu YL, Wei CW, Chen YL, Chen MH, Yiang GT: Immunotherapy of breast cancer by single delivery with rAAV2-mediated interleukin-15 expression. Int J Oncol. 2010, 36:365-370.
• [22]Yu YL, Yu SL, Su KJ, Wei CW, Jian MH, Lin PC, Tseng IH, Lin CC, Su CC, Chan DC, Lin SZ, Harn HJ, Chen YL: Extended O6-methylguanine methyltransferase promoter hypermethylation following n-butylidenephthalide combined with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) on inhibition of human hepatocellular carcinoma cell growth. J Agric Food Chem 2010, 58:1630-1638.
• [23]Newman DJ, Cragg GM, Holbeck S, Sausville EA: Natural products and derivatives as leads to cell cycle pathway targets in cancer chemotherapy. Curr Cancer Drug Targets 2002, 2:279-308.
• [24]Weng XY, Ma RD, Yu LJ: Apoptosis of human nasopharyngeal carcinoma CNE-2Z cells induced by tubeimoside I. Ai Zheng. 2003, 22:806-811.
• [25]Wang X, Xia X, Xu C, Xu J, Wang P, Xiang J, Bai D, Leung AW: Ultrasound-induced cell death of nasopharyngeal carcinoma cells in the presence of curcumin. Integr Cancer Ther. 2011, 10:70-76.
• [26]Kim J, Yu W, Kovalski K, Ossowski L: Requirement for specific proteases in cancer cell intravasation as revealed by a novel semiquantitative PCR-based assay. Cell 1998, 94:353-362.
• [27]Itoh T, Tanioka M, Matsuda H, Nishimoto H, Yoshioka T, Suzuki R, Uehira M: Experimental metastasis is suppressed in MMP-9- deficient mice. Clin Exp Metastasis 1999, 17:177-181.
• [28]He JR, Qin H, Ren ZF, Cui C, Zhang Y, Ranatunga D, Zeng YX, Jia WH: MMP-9 expression in peripheral blood mononuclear cells and the association with clinicopathological features and prognosis of nasopharyngeal carcinoma. Clin Chem Lab Med. 2011, 49:705-710.
• [29]Horikawa T, Yoshizaki T, Sheen TS, Lee SY, Furukawa M: Association of latent membrane protein 1 and matrix metalloproteinase 9 with metastasis in nasopharyngeal carcinoma. Cancer 2000, 89:715-723.
• [30]Guruvayoorappan C: Amentoflavone inhibits experimental tumor metastasis through a regulatory mechanism involving MMP-2, MMP-9, prolyl hydroxylase, lysyl oxidase, VEGF, ERK-1, ERK-2, STAT-1, nm23 and cytokines in lung tissues of C57BL/6 mice. Immunopharmacol Immunotoxicol 2008, 30:711-727.
• [31]Waas ET: Matrix metalloproteinase 2 and 9 activity in patients with colorectal cancer liver metastasis. Br J Surg 2003, 90:1556-1564.
• [32]Okada N: Matrix metalloproteinase-2 and −9 in bile as a marker of liver metastasis in colorectal cancer. Biochem Biophys Res Commun 2001, 288:212-216.
• [33]Itoh Y, Nagase H: Matrix metalloproteinases in cancer. Essays Biochem 2002, 38:21-36.
• [34]Liu JF, Cre’pin M, Liu JM, Barritault D, Ledoux D: FGF-2 and TPA induce matrix metalloproteinase-9 secretion in MCF-7 cells through PKC activation of the Ras/ERK pathway. Biochem Biophys Res Commun 2002, 293:1174-1182.
• [35]Mitra SK, Hanson DA, Schlaepfer DD: Focal adhesion kinase: in command and control of cell motility. Nat Rev Mol Cell Biol 2005, 6:56-68.
• [36]Schlaepfer DD, Hunter T: Focal adhesion kinase overexpression enhances ras-dependent integrin signaling to ERK2/mitogen-activated protein kinase through interactions with and activation of c-Src. J Biol Chem 1997, 272:13189-13195.
• [37]Liu P, Kimmoun E, Legrand A, Sauvanet A, Degott C, Lardeux B, Bernuau D: Activation of NF-kappa B, AP-1 and STAT transcription factors is a frequent and early event in human hepatocellular carcinomas. J Hepatol 2002, 37:63-71.
• [38]Simon C, Goepfert H, Boyd D: Inhibition of the p38 mitogen-activated protein kinase by SB 203580 blocks PMA-induced Mr 92,000 type IV collagenase secretion and in vitro invasion. Cancer Res 1998, 58:1135-1139.
• [39]Genersch E, Hayess K, Neuenfeld Y, Haller H: Sustained ERK phosphorylation is necessary but not sufficient for MMP-9 regulation in endothelial cells: involvement of Ras-dependent and -independent pathways. J Cell Sci 2000, 113:4319-4330.
• [40]Shin M, Yan C, Boyd D: An inhibitor of c-jun aminoterminal kinase (SP600125) represses c-Jun activation, DNA-binding, and PMA-inducible 92-kDa type IV collagenase expression. Biochim Biophys Acta 2002, 1589:311-316.
• [41]Yang JW, Pokharel YR, Kim MR, Woo ER, Choi HK, Kang KW: Inhibition of inducible nitric oxide synthase by sumaflavone isolated from Selaginella tamariscina. J Ethnopharmacol 2006, 105:107-113.
• [42]Bronner C, Landry Y: Kinetics of the inhibitory effect of flavonoids on histamine secretion from mast cells. Agents Actions 1985, 16:147-151.
• [43]He J, Xu Q, Wang M, Li C, Qian X, Shi Z, Liu LZ, Jiang BH: Oral administration of apigenin inhibits metastasis through AKT/P70S6K1/MMP-9 pathway in orthotopic ovarian tumor model. Int J Mol Sci 2012, 13:7271-7282.
• [44]Liao YF, Rao YK, Tzeng YM: Aqueous extract of Anisomeles indica and its purified compound exerts anti-metastatic activity through inhibition of NF-κB/AP-1-dependent MMP-9 activation in human breast cancer MCF-7 cells. Food Chem Toxicol 2012, 50:2930-2936.
• [45]Oozes ON, Mayo LD, Gustin JA, Pfeffer SR, Pfeffer LM, Donner DB: NF-kappaB activation by tumor necrosis factor requires the Skt serine–threonine kinase. Nature 1999, 401:82-85.
• [46]Ruiz PA, Haller D: Functional diversity of flavonoids in the inhibition of the proinflammatory NF-κB, IRF, and Akt signaling pathways in murine intestinal epithelial cells. J Nutr 2006, 136:664-671.