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Cancer Chemotherapy and Pharmacology

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01-12-2015 | Original Article

Evodiamine inhibits the migration and invasion of nasopharyngeal carcinoma cells in vitro via repressing MMP-2 expression

Authors: Xianbing Peng, Qun Zhang, Yi Zeng, Jin Li, Lixin Wang, Ping Ai

Published in: Cancer Chemotherapy and Pharmacology | Issue 6/2015

Abstract

Purpose

Evodiamine is one of active alkaloids isolated from the traditional Chinese medicine Evodia rutaecarpa Bentham and has various pharmacological properties. In this study, we investigated its effects on the migration, invasion, and associated mechanism in human nasopharyngeal carcinoma (NPC) cells.

Methods

Cell viability was determined by MTT assay after evodiamine treatment. Wound-healing assay and Boyden transwell system were used to evaluate the inhibitory effects of evodiamine on cell migration and invasion. MMP-2/9 activity was determined using commercial detection kits. The levels of associated proteins involved in the regulation of cell migration and invasion were analyzed by Western blotting.

Results

Evodiamine effectively inhibited the migration and invasion of HONE1 and CNE1 cells, and hardly affected cell proliferation, but significantly suppressed cell adhesion activity in vitro. Additionally, evodiamine treatment significantly decreased mRNA and protein levels of MMP-2 and its activity in the NPC cells, but had little effects on MMP-9 mRNA and protein levels and its activity. Further investigation revealed that evodiamine inhibited the translocation of NF-κB p65, which involves the regulation of MMP-2 expression in cancer invasion. Additionally, evodiamine treatment did not significantly affect the protein levels of JNK, p38, Akt, and their phosphorylated forms and ERK1/2, but strongly attenuated ERK1/2 phosphorylation level, which at least partly accounts for the signal pathway of evodiamine-inhibited migration and invasion of NPC cells.

Conclusion

These findings demonstrate that evodiamine inhibits the migration and invasiveness of NPC cells, and it is probably a potential agent for the treatment of NPC invasion and metastasis.

Pan Y, Zhang Q, Atsaves V, Yang H, Claret FX (2013) Suppression of Jab1/CSN5 induces radio- and chemo-sensitivity in nasopharyngeal carcinoma through changes to the DNA damage and repair pathways. Oncogene 32:2756–2766PubMedCentralCrossRefPubMed

Chia WK, Wang WW, Teo M, Tai WM, Lim WT, Tan EH, Leong SS, Sun L, Chen JJ, Gottschalk S, Toh HC (2012) A phase II study evaluating the safety and efficacy of an adenovirus-ΔLMP1-LMP2 transduced dendritic cell vaccine in patients with advanced metastatic nasopharyngeal carcinoma. Ann Oncol 23:997–1005PubMedCentralCrossRefPubMed

Lo KW, Chung GT, To KF (2012) Deciphering the molecular genetic basis of NPC through molecular, cytogenetic, and epigenetic approaches. Semin Cancer Biol 22:79–86CrossRefPubMed

Pan Y, Claret FX (2012) Targeting Jab1/CSN5 in nasopharyngeal carcinoma. Cancer Lett 326:155–160PubMedCentralCrossRefPubMed

Tao Q, Chan AT (2007) Nasopharyngeal carcinoma: molecular pathogenesis and therapeutic developments. Expert Rev Mol Med 9:1–24CrossRefPubMed

Ma BB, Hui EP, Chan AT (2008) Systemic approach to improving treatment outcome in nasopharyngeal carcinoma: current and future directions. Cancer Sci 99:1311–1318CrossRefPubMed

Siegel R, Ward E, Brawley O, Jemal A (2011) Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin 61:212–236CrossRefPubMed

Sung HJ, Kim Y, Kang H, Sull JW, Kim YS, Jang SW, Ko J (2012) Inhibitory effect of Trolox on the migration and invasion of human lung and cervical cancer cells. Int J Mol Med 29:245–251PubMed

Curran S, Murray GI (2000) Matrix metalloproteinases: molecular aspects of their roles in tumour invasion and metastasis. Eur J Cancer 36:1621–1630CrossRefPubMed

10.

Lirdprapamongkol K, Sakurai H, Kawasaki N, Choo MK, Saitoh Y, Aozuka Y, Singhirunnusorn P, Ruchirawat S, Svasti J, Saiki I (2005) Vanillin suppresses in vitro invasion and in vivo metastasis of mouse breast cancer cells. Eur J Pharm Sci 25:57–65CrossRefPubMed

11.

Yang SF, Hsieh YS, Lin CL, Hsu NY, Chiou HL, Chou FP, Chu SC (2005) Increased plasma levels of urokinase plasminogen activator and matrix metalloproteinase-9 in nonsmall cell lung cancer patients. Clin Chim Acta 354:91–99CrossRefPubMed

12.

Wang Z, Sun L, Yu H, Zhang Y, Gong W, Jin H, Zhang L, Liang H (2012) Binding mode prediction of evodiamine within vanilloid receptor TRPV1. Int J Mol Sci 13:8958–8969PubMedCentralCrossRefPubMed

13.

Yu ZK, Wright JT, Hausman GJ (1997) Preadipocyte recruitment in stromal vascular cultures after depletion of committed preadipocytes by immunocytotoxicity. Obes Res 5:9–15CrossRefPubMed

14.

Bak EJ, Park HG, Kim JM, Kim JM, Yoo YJ, Cha JH (2010) Inhibitory effect of evodiamine alone and in combination with rosiglitazone on in vitro adipocyte differentiation and in vivo obesity related to diabetes. Int J Obes 34:250–260CrossRef

15.

Yu H, Jin H, Gong W, Wang Z, Liang H (2013) Pharmacological actions of multi-target -directed evodiamine. Molecules 18:1826–1843CrossRefPubMed

16.

Wang T, Kusudo T, Takeuchi T, Yamashita Y, Kontani Y, Okamatsu Y, Saito M, Mori N, Yamashita H (2013) Evodiamine inhibits insulin-stimulated mTOR-S6K activation and IRS1 serine phosphorylation in adipocytes and improves glucose tolerance in obese/diabetic mice. PLoS ONE 8:e83264PubMedCentralCrossRefPubMed

17.

Rasul A, Yu B, Zhong L, Khan M, Yang H, Ma T (2012) Cytotoxic effect of evodiamine in SGC-7901 human gastric adenocarcinoma cells via simultaneous induction of apoptosis and autophagy. Oncol Rep 27:1481–1487PubMed

18.

Hong JY, Park SH, Min HY, Park HJ, Lee SK (2014) Anti-proliferative effects of evodiamine in human lung cancer cells. J Cancer Prev 19:7–13PubMedCentralCrossRefPubMed

19.

Bai X, Meng H, Ma L, Guo A (2015) Inhibitory effects of evodiamine on human osteosarcoma cell proliferation and apoptosis. Oncol Lett 9:801–805PubMedCentralPubMed

20.

Du J, Wang XF, Zhou QM, Zhang TL, Lu YY, Zhang H, Su SB (2013) Evodiamine induces apoptosis and inhibits metastasis in MDA-MB-231 human breast cancer cells in vitro and in vivo. Oncol Rep 30:685–694PubMed

21.

Takada Y, Kobayashi Y, Aggarwal BB (2005) Evodiamine abolishes constitutive and inducible NF-kappaB activation by inhibiting IkappaBalpha kinase activation, thereby suppressing NF-kappaB-regulated antiapoptotic and metastatic gene expression, up-regulating apoptosis, and inhibiting invasion. J Biol Chem 280:17203–17212CrossRefPubMed

22.

Ogasawara M, Matsubara T, Suzuki H (2001) Inhibitory effects of evodiamine on in vitro invasion and experimental lung metastasis of murine colon cancer cells. Biol Pharm Bull 24:917–920CrossRefPubMed

23.

Yan YY, Bai JP, Xie Y, Yu JZ, Ma CG (2013) The triterpenoid pristimerin induces U87 glioma cell apoptosis through reactive oxygen species-mediated mitochondrial dysfunction. Oncol Lett 5:242–248PubMedCentralPubMed

24.

Doi Y, Yashiro M, Yamada N, Amano R, Noda S, Hirakawa K (2012) VEGF-A/VEGFR-2 signaling plays an important role for the motility of pancreas cancer cells. Ann Surg Oncol 19:2733–2743CrossRefPubMed

25.

Zeng GF, Cai SX, Wu GJ (2011) Up-regulation of METCAM/MUC18 promotes motility, invasion, and tumorigenesis of human breast cancer cells. BMC Cancer 11:113PubMedCentralCrossRefPubMed

26.

Li L, Chen P, Ling Y, Song X, Lu Z, He Q, Li Z, Lu N, Guo Q (2011) Inhibitory effects of GL-V9 on the invasion of human breast carcinoma cells by downregulation the expression and activity of matrix metalloproteinase-2/9. Eur J Pharm Sci 43:393–399CrossRefPubMed

27.

Johnson SL, Chen LH, Harbach R, Sabet M, Savinov A, Cotton NJ, Strongin A, Guiney D, Pellecchia M (2008) Rhodanine derivatives as selective protease inhibitors against bacterial toxins. Chem Biol Drug Des 71:131–139CrossRefPubMed

28.

Wang Z, Banerjee S, Li Y, Rahman KM, Zhang Y, Sarkar FH (2006) Down-regulation of notch-1 inhibits invasion by inactivation of nuclear factor-kappaB, vascular endothelial growth factor, and matrix metalloproteinase-9 in pancreatic cancer cells. Cancer Res 66:2778–2784CrossRefPubMed

29.

Zheng H, Takahashi H, Murai Y, Cui Z, Nomoto K, Niwa H, Tsuneyama K, Takano Y (2006) Expression of MMP-2, MMP-9 and VEGF are closely linked to growth, invasion, metastasis and angiogenesis of gastric carcinoma. Anticancer Res 26:3579–3583PubMed

30.

Farina AR, Cappabianca L, DeSantis G, Di Ianni N, Ruggeri P, Ragone M, Merolle S, Tonissen KF, Gulino A, Mackay AR (2011) Thioredoxin stimulates MMP-9 expression, de-regulates the MMP-9/TIMP-1 equilibrium and promotes MMP-9 dependent invasion in human MDA-MB-231 breast cancer cells. FEBS Lett 585:3328–3336CrossRefPubMed

31.

Lu Y, Hong TG, Jin M, Yang JH, Suh SJ, Piao DG, Ko HK, Seo CS, Chang YC, Kim CH, Son JK, Chang HW (2010) Saucerneol G, a new lignan, from Saururus chinensis inhibits matrix metalloproteinase-9 induction via a nuclear factor κB and mitogen activated protein kinases in lipopolysaccharide-stimulated RAW264.7 cells. Biol Pharm Bull 33:1944–1948CrossRefPubMed

32.

Park SK, Hwang YS, Park KK, Park HJ, Seo JY, Chung WY (2009) Kalopanaxsaponin A inhibits PMA-induced invasion by reducing matrix metalloproteinase-9 via PI3K/Akt- and PKCdelta-mediated signaling in MCF-7 human breast cancer cells. Carcinogenesis 30:1225–1233CrossRefPubMed

33.

Cao JY, Liu L, Chen SP, Zhang X, Mi YJ, Liu ZG, Li MZ, Zhang H, Qian CN, Shao JY, Fu LW, Xia YF, Zeng MS (2010) Prognostic significance and therapeutic implications of centromere protein F expression in human nasopharyngeal carcinoma. Mol Cancer 9:237PubMedCentralCrossRefPubMed

34.

Zhang Z, Zhu W, Zhang J, Guo L (2011) Tyrosine kinase Etk/BMX protects nasopharyngeal carcinoma cells from apoptosis induced by radiation. Cancer Biol Ther 11:690–698CrossRefPubMed

35.

Lee TJ, Kim EJ, Kim S, Jung EM, Park JW, Jeong SH, Park SE, Yoo YH, Kwon TK (2006) Caspase-dependent and caspase-independent apoptosis induced by evodiamine in human leukemic U937 cells. Mol Cancer Ther 5:2398–2407CrossRefPubMed

36.

Ogasawara M, Matsunaga T, Takahashi S, Saiki I, Suzuki H (2002) Anti-invasive and metastatic activities of evodiamine. Biol Pharm Bull 25:1491–1493CrossRefPubMed

37.

Shyu KG, Lin S, Lee CC, Chen E, Lin LC, Wang BW, Tsai SC (2006) Evodiamine inhibits in vitro angiogenesis: implication for antitumorgenicity. Life Sci 78:2234–2243CrossRefPubMed

38.

Ogasawara M, Suzuki H (2004) Inhibition by evodiamine of hepatocyte growth factor-induced invasion and migration of tumor cells. Biol Pharm Bull 27:578–582CrossRefPubMed

39.

Lin ML, Chung JG, Lu YC, Yang CY, Chen SS (2009) Rhein inhibits invasion and migration of human nasopharyngeal carcinoma cells in vitro by down-regulation of matrix metalloproteinases-9 and vascular endothelial growth factor. Oral Oncol 45:531–537CrossRefPubMed

40.

Köhrmann A, Kammerer U, Kapp M, Dietl J, Anacker J (2009) Expression of matrix metalloproteinases (MMPs) in primary human breast cancer and breast cancer cell lines: new findings and review of the literature. BMC Cancer 9:188PubMedCentralCrossRefPubMed

41.

Kang H, Jang SW, Ko J (2011) Human leucine zipper protein sLZIP induces migration and invasion of cervical cancer cells via expression of matrix metalloproteinase-9. J Biol Chem 286:42072–42081PubMedCentralCrossRefPubMed

42.

Sun XJ, Zhang P, Li HH, Jiang ZW, Jiang CC, Liu H (2014) Cisplatin combined with metformin inhibits migration and invasion of human nasopharyngeal carcinoma cells by regulating E-cadherin and MMP-9. Asian Pac J Cancer Prev 15:4019–4023CrossRefPubMed

43.

Sun W, Liu DB, Li WW, Zhang LL, Long GX, Wang JF, Mei Q, Hu GQ (2014) Interleukin-6 promotes the migration and invasion of nasopharyngeal carcinoma cell lines and upregulates the expression of MMP-2 and MMP-9. Int J Oncol 44:1551–1560PubMed

44.

Prabhu L, Mundade R, Korc M, Loehrer PJ, Lu T (2014) Critical role of NF-κB in pancreatic cancer. Oncotarget 5:10969–10975PubMedCentralCrossRefPubMed

45.

Noma N, Asagiri M, Takeiri M, Ohmae S, Takemoto K, Iwaisako K, Minato N, Maeda-Yamamoto M, Simizu S, Umezawa K (2015) Inhibition of MMP-2-mediated mast cell invasion by NF-κB inhibitor DHMEQ in mast cells. Int Arch Allergy Immunol 166:84–90CrossRefPubMed

46.

Zhou X, Yang J, Wang Y, Li W, Li-Ling J, Deng Y, Zhang M (2012) Cucurbitacin B inhibits 12-O-tetradecanoylphorbol 13-acetate-induced invasion and migration of human hepatoma cells through inactivating mitogen-activated protein kinase and PI3K/Akt signal transduction pathways. Hepatol Res 42:5401–5411CrossRef

47.

Hwang YP, Yun HJ, Kim HG, Han EH, Lee GW, Jeong HG (2010) Suppression of PMA-induced tumor cell invasion by dihydroartemisinin via inhibition of PKC alpha/Raf/MAPKs and NF-kappaB/AP-1-dependent mechanisms. Biochem Pharmacol 79:1714–1726CrossRefPubMed

48.

You J, Mi D, Zhou X, Qiao L, Zhang H, Zhang X, Ye L (2009) A positive feedback between activated extracellularly regulated kinase and cyclooxygenase/lipoxygenase maintains proliferation and migration of breast cancer cells. Endocrinology 150:1607–1617CrossRefPubMed

49.

Yeh CB, Hsieh MJ, Hsieh YH, Chien MH, Chiou HL, Yang SF (2012) Antimetastatic effects of norcantharidin on hepatocellular carcinoma by transcriptional inhibition of MMP-9 through modulation of NF-kB activity. PLoS ONE 7:e31055PubMedCentralCrossRefPubMed

Title: Evodiamine inhibits the migration and invasion of nasopharyngeal carcinoma cells in vitro via repressing MMP-2 expression
Authors: Xianbing Peng
Qun Zhang
Yi Zeng
Jin Li
Lixin Wang
Ping Ai
Publication date: 01-12-2015
Publisher: Springer Berlin Heidelberg
Published in: Cancer Chemotherapy and Pharmacology / Issue 6/2015
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-015-2902-9

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Purpose

Methods

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