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Diosmetin inhibits the metastasis of hepatocellular carcinoma cells by downregulating the expression levels of MMP‑2 and MMP‑9

  • Authors:
    • Jie Liu
    • Xiaojun Wen
    • Bin Liu
    • Qingyu Zhang
    • Jingjing Zhang
    • Huilai Miao
    • Runzhi Zhu
  • View Affiliations / Copyright

    Affiliations: Laboratory of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang Key Laboratory of Hepatobiliary Diseases, Zhanjiang, Guangdong 524001, P.R. China
    Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2401-2408
    |
    Published online on: February 5, 2016
       https://doi.org/10.3892/mmr.2016.4872
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Abstract

Hepatocellular carcinoma (HCC) is one of the most malignant types of tumor worldwide with a high rate of mortality. Diosmetin (DIOS) exhibits various activities, including anticancer activities. However, the role of DIOS in the metastasis of HCC, and its underlying molecular mechanism, remain to be fully elucidated. In the present study, the antimetastatic effects of DIOS were investigated in SK‑HEP‑1 and MHcc97H HCC cell lines. Cell proliferation, wound healing, motility, invasion and adhesion capacities were examined to evaluate the inhibitory effect of DIOS on the metastasis of HCC cells. Cell viability was detected using an MTT assay in order to verify the inhibitory effect of DIOS on the proliferation of HCC cells. Cell migration was assessed using would healing and motility assays in order to verify the inhibitory effect of DIOS on the migration of HCC cells. Cell invasion and adhesion assays were performed in order to verify the inhibitory effect of DIOS on the invasion and adhesion of HCC cells. Matrix metalloproteinase (MMP)‑2/9, proteins of the mitogen‑activated protein kinase (MAPK) pathway (c‑Jun N‑terminal kinase, extracellular signal‑regulated kinase and p38 MAPK) and protein kinase C‑δ were detected in order to verify the potential molecular mechanisms of DIOS in the inhibition of the metastasis of HCC cells. DIOS was observed to inhibit the metastasis of SK‑HEP‑1 and MHcc97H cells by downregulating the expression of MMP‑2/9 via the PKC/MAPK/MMP pathways. DIOS also inhibited the migration and invasion of the HCC cells, and may serve as a potential candidate agent for the prevention of HCC metastasis.
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1 

Feng M, Gao W, Wang R, Chen W, Man YG, Figg WD, Wang XW, Dimitrov DS and Ho M: Therapeutically targeting glypican-3 via a conformation-specific single-domain antibody in hepatocellular carcinoma. Proc Natl Acad Sci USA. 110:E1083–E1091. 2013. View Article : Google Scholar : PubMed/NCBI

2 

Zhang Q, Liu J, Liu B, Xia J, Chen N, Chen X, Cao Y, Zhang C, Lu C, Li M and Zhu R: Dihydromyricetin promotes hepatocellular carcinoma regression via a p53 activation-dependent mechanism. Sci Rep. 4:46282014.PubMed/NCBI

3 

Zhang QY, Li R, Zeng GF, Liu B, Liu J, Shu Y, Liu ZK, Qiu ZD, Wang DJ, Miao HL, et al: Dihydromyricetin inhibits migration and invasion of hepatoma cells through regulation of MMP-9 expression. World J Gastroenterol. 20:10082–10093. 2014. View Article : Google Scholar : PubMed/NCBI

4 

Hsieh MJ, Lin CW, Yang SF, Chen MK and Chiou HL: Glabridin inhibits migration and invasion by transcriptional inhibition of matrix metalloproteinase 9 through modulation of NF-κB and AP-1 activity in human liver cancer cells. Br J Pharmacol. 171:3037–3050. 2014. View Article : Google Scholar : PubMed/NCBI

5 

Chen TY, Li YC, Liu YF, Tsai CM, Hsieh YH, Lin CW, Yang SF and Weng CJ: Role of MMP14 gene polymorphisms in susceptibility and pathological development to hepatocellular carcinoma. Ann Surg Oncol. 18:2348–2356. 2011. View Article : Google Scholar : PubMed/NCBI

6 

Alexander SP, Benson HE, Faccenda E, Pawson AJ, Sharman JL, McGrath JC, Catterall WA, Spedding M, Peters JA, Harmar AJ, et al: The Concise Guide to PHARMACOLOGY 2013/14: Overview. Br J Pharmacol. 170:1449–1458. 2013. View Article : Google Scholar

7 

Spanakis M, Kasmas S and Niopas I: Simultaneous determination of the flavonoid aglycones diosmetin and hesperetin in human plasma and urine by a validated GC/MS method: In vivo metabolic reduction of diosmetin to hesperetin. Biomed Chromatogr. 23:124–131. 2009. View Article : Google Scholar

8 

Chan BC, Ip M, Gong H, Lui SL, See RH, Jolivalt C, Fung KP, Leung PC, Reiner NE and Lau CB: Synergistic effects of diosmetin with erythromycin against ABC transporter over-expressed methicillin-resistant Staphylococcus aureus1 (MRSA) RN4220/pUL5054 and inhibition of MRSA pyruvate kinase. Phytomedicine. 20:611–614. 2013. View Article : Google Scholar : PubMed/NCBI

9 

Meng JC, Zhu QX and Tan RX: New antimicrobial mono-and sesquiterpenes from Soroseris hookeriana subsp. erysimoides. Planta Med. 66:541–544. 2000. View Article : Google Scholar : PubMed/NCBI

10 

Chandler D, Woldu A, Rahmadi A, Shanmugam K, Steiner N, Wright E, Benavente-García O, Schulz O, Castillo J and Münch G: Effects of plant-derived polyphenols on TNF-alpha and nitric oxide production induced by advanced glycation endproducts. Mol Nutr Food Res. 54(Suppl 2): S141–S150. 2010. View Article : Google Scholar : PubMed/NCBI

11 

Liao W, Ning Z, Chen L, Wei Q, Yuan E, Yang J and Ren J: Intracellular antioxidant detoxifying effects of diosmetin on 2, 2-azobis (2-amidinopropane) dihydrochloride (AAPH)-induced oxidative stress through inhibition of reactive oxygen species generation. J Agric Food Chem. 62:8648–8654. 2014. View Article : Google Scholar : PubMed/NCBI

12 

Androutsopoulos VP, Mahale S, Arroo RR and Potter G: Anticancer effects of the flavonoid diosmetin on cell cycle progression and proliferation of MDA-MB 468 breast cancer cells due to CYP1 activation. Oncol Rep. 21:1525–1528. 2009.PubMed/NCBI

13 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2–ΔΔCt method. Methods. 25:402–408. 2001. View Article : Google Scholar

14 

Liu J, Shu Y, Zhang Q, Liu B, Xia J, Qiu M, Miao H, Li M and Zhu R: Dihydromyricetin induces apoptosis and inhibits proliferation in hepatocellular carcinoma cells. Oncol Lett. 8:1645–1651. 2014.PubMed/NCBI

15 

Chen H, Gao Y, Wu J, Chen Y, Chen B, Hu J and Zhou J: Exploring therapeutic potentials of baicalin and its aglycone baicalein for hematological malignancies. Cancer Lett. 354:5–11. 2014. View Article : Google Scholar : PubMed/NCBI

16 

Zeng G, Liu J, Chen H, Liu B, Zhang Q, Li M and Zhu R: Dihydromyricetin induces cell cycle arrest and apoptosis in melanoma SK-MEL-28 cells. Oncol Rep. 31:2713–2719. 2014.PubMed/NCBI

17 

Liu B, Zhou Z, Zhou W, Liu J, Zhang Q, Xia J, Liu J, Chen N, Li M and Zhu R: Resveratrol inhibits proliferation in human colorectal carcinoma cells by inducing G1/S-phase cell cycle arrest and apoptosis through caspase/cyclin-CDK pathways. Mol Med Rep. 10:1697–1702. 2014.PubMed/NCBI

18 

Androutsopoulos VP and Spandidos DA: The flavonoids diosmetin and luteolin exert synergistic cytostatic effects in human hepatoma HepG2 cells via CYP1A-catalyzed metabolism, activation of JNK and ERK and P53/P21 up-regulation. J Nutr Biochem. 24:496–504. 2013. View Article : Google Scholar

19 

Kwon M, Lee SJ, Wang Y, Rybak Y, Luna A, Reddy S, Adem A, Beaty BT, Condeelis JS and Libutti SK: Filamin A interacting protein 1-like inhibits WNT signaling and MMP expression to suppress cancer cell invasion and metastasis. Int J Cancer. 135:48–60. 2014. View Article : Google Scholar :

20 

Elkington PT and Friedland JS: Matrix metalloproteinases in destructive pulmonary pathology. Thorax. 61:259–266. 2006. View Article : Google Scholar

21 

Chen T, Li M, Zhang R and Wang H: Dihydroartemisinin induces apoptosis and sensitizes human ovarian cancer cells to carboplatin therapy. J Cell Mol Med. 13:1358–1370. 2009. View Article : Google Scholar

22 

Hurst DR and Welch DR: Metastasis suppressor genes at the interface between the environment and tumor cell growth. Int Rev Cell Mol Biol. 286:107–180. 2011. View Article : Google Scholar : PubMed/NCBI

23 

Lin CW, Shen SC, Chien CC, Yang LY, Shia LT and Chen YC: 12-O-tetradecanoylphorbol-13-acetate-induced invasion/migration of glioblastoma cells through activating PKCalpha/ERK/NF-kappaB-dependent MMP-9 expression. J Cell Physiol. 225:472–481. 2010. View Article : Google Scholar : PubMed/NCBI

24 

Hidalgo M and Eckhardt SG: Development of matrix metal-loproteinase inhibitors in cancer therapy. J Natl Cancer Inst. 93:178–193. 2001. View Article : Google Scholar : PubMed/NCBI

25 

Hwang YP, Yun HJ, Kim HG, Han EH, Lee GW and Jeong HG: Suppression of PMA-induced tumor cell invasion by dihydroartemisinin via inhibition of PKCalpha/Raf/MAPKs and NF-kappaB/AP-1-dependent mechanisms. Biochem Pharmacol. 79:1714–1726. 2010. View Article : Google Scholar : PubMed/NCBI

26 

He Q, Zhou X, Li S, Jin Y, Chen Z, Chen D, Cai Y, Liu Z, Zhao T and Wang A: MicroRNA-181a suppresses salivary adenoid cystic carcinoma metastasis by targeting MAPK-Snai2 pathway. Biochim Biophys Acta. 1830:5258–5266. 2013. View Article : Google Scholar : PubMed/NCBI

27 

Woo JH, Lim JH, Kim YH, Suh SI, Min DS, Chang JS, Lee YH, Park JW and Kwon TK: Resveratrol inhibits phorbol myristate acetate-induced matrix metalloproteinase-9 expression by inhibiting JNK and PKC delta signal transduction. Oncogene. 23:1845–1853. 2003. View Article : Google Scholar : PubMed/NCBI

28 

Reunanen N, Westermarck J, Häkkinen L, Holmström TH, Elo I, Eriksson JE and Kähäri VM: Enhancement of fibroblast collagenase (matrix metalloproteinase-1) gene expression by ceramide is mediated by extracellular signal-regulated and stress-activated protein kinase pathways. J Biol Chem. 273:5137–5145. 1998. View Article : Google Scholar : PubMed/NCBI

29 

Mauro LV, Grossoni VC, Urtreger AJ, Yang C, Colombo LL, Morandi A, Pallotta MG, Kazanietz MG, Bal de Kier Joffé ED and Puricelli LL: PKC Delta (PKCdelta) promotes tumoral progression of human ductal pancreatic cancer. Pancreas. 39:e31–e41. 2010. View Article : Google Scholar

30 

Hu CT, Cheng CC, Pan SM, Wu JR and Wu WS: PKC mediates fluctuant ERK-paxillin signaling for hepatocyte growth factor-induced migration of hepatoma cell HepG2. Cell Signal. 25:1457–1467. 2013. View Article : Google Scholar : PubMed/NCBI

31 

Hu CT, Wu JR, Cheng CC, Wang S, Wang HT, Lee MC, Wang LJ, Pan SM, Chang TY and Wu WS: Reactive oxygen species-mediated PKC and integrin signaling promotes tumor progression of human hepatoma HepG2. Clin Exp Metastasis. 28:851–863. 2011. View Article : Google Scholar : PubMed/NCBI

32 

Hsieh HL, Wu CY and Yang CM: Bradykinin induces matrix metalloproteinase-9 expression and cell migration through a PKC-delta-dependent ERK/Elk-1 pathway in astrocytes. Glia. 56:619–632. 2008. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Liu J, Wen X, Liu B, Zhang Q, Zhang J, Miao H and Zhu R: Diosmetin inhibits the metastasis of hepatocellular carcinoma cells by downregulating the expression levels of MMP‑2 and MMP‑9. Mol Med Rep 13: 2401-2408, 2016.
APA
Liu, J., Wen, X., Liu, B., Zhang, Q., Zhang, J., Miao, H., & Zhu, R. (2016). Diosmetin inhibits the metastasis of hepatocellular carcinoma cells by downregulating the expression levels of MMP‑2 and MMP‑9. Molecular Medicine Reports, 13, 2401-2408. https://doi.org/10.3892/mmr.2016.4872
MLA
Liu, J., Wen, X., Liu, B., Zhang, Q., Zhang, J., Miao, H., Zhu, R."Diosmetin inhibits the metastasis of hepatocellular carcinoma cells by downregulating the expression levels of MMP‑2 and MMP‑9". Molecular Medicine Reports 13.3 (2016): 2401-2408.
Chicago
Liu, J., Wen, X., Liu, B., Zhang, Q., Zhang, J., Miao, H., Zhu, R."Diosmetin inhibits the metastasis of hepatocellular carcinoma cells by downregulating the expression levels of MMP‑2 and MMP‑9". Molecular Medicine Reports 13, no. 3 (2016): 2401-2408. https://doi.org/10.3892/mmr.2016.4872
Copy and paste a formatted citation
x
Spandidos Publications style
Liu J, Wen X, Liu B, Zhang Q, Zhang J, Miao H and Zhu R: Diosmetin inhibits the metastasis of hepatocellular carcinoma cells by downregulating the expression levels of MMP‑2 and MMP‑9. Mol Med Rep 13: 2401-2408, 2016.
APA
Liu, J., Wen, X., Liu, B., Zhang, Q., Zhang, J., Miao, H., & Zhu, R. (2016). Diosmetin inhibits the metastasis of hepatocellular carcinoma cells by downregulating the expression levels of MMP‑2 and MMP‑9. Molecular Medicine Reports, 13, 2401-2408. https://doi.org/10.3892/mmr.2016.4872
MLA
Liu, J., Wen, X., Liu, B., Zhang, Q., Zhang, J., Miao, H., Zhu, R."Diosmetin inhibits the metastasis of hepatocellular carcinoma cells by downregulating the expression levels of MMP‑2 and MMP‑9". Molecular Medicine Reports 13.3 (2016): 2401-2408.
Chicago
Liu, J., Wen, X., Liu, B., Zhang, Q., Zhang, J., Miao, H., Zhu, R."Diosmetin inhibits the metastasis of hepatocellular carcinoma cells by downregulating the expression levels of MMP‑2 and MMP‑9". Molecular Medicine Reports 13, no. 3 (2016): 2401-2408. https://doi.org/10.3892/mmr.2016.4872
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