Erratum: "Dioscorea nipponica Attenuates Migration and Invasion by Inhibition of Urokinase-Type Plasminogen Activator through Involving PI3K/Akt and Transcriptional Inhibition of NF-[Formula: see text]B and SP-1 in Hepatocellular Carcinoma".

High mortality and morbidity rates for hepatocellular carcinoma (HCC) in Taiwan primarily result from uncontrolled tumor metastasis. In our previous studies, we have reported that Dioscorea nipponica Makino extract (DNE) has anti-metastasis effects on human oral cancer cells. However, the effect of DNE on hepatoma metastasis have not been thoroughly investigated and remains poorly understood. To determine the effects of DNE on the migration and invasion in HCC cells we used a wound healing model, Boyden chamber assays, gelatin/casein zymography and Western blotting. Transcriptional levels of matrix metalloproteinase-9 (MMP-9) and urokinase-type plasminogen activator (u-PA) were detected by real-time PCR and promoter assays. In this study, DNE treatment significantly inhibited the migration/invasion capacities of Huh7 cell lines. The results of gelatin/casein zymography and Western blotting revealed that the activities and protein levels of the MMP-9 and u-PA were inhibited by DNE. Tests of the mRNA levels, real-time PCR, and promoter assays evaluated the inhibitory effects of DNE on u-PA expression in human hepatoma cells. A chromatin immunoprecipitation (ChIP) assay showed not only that DNE inhibits u-PA expression, but also the inhibitory effects were associated with the down-regulation of the transcription factors of NF-κB and SP-1 signaling pathways. Western blot analysis also showed that DNE inhibits PI3K and phosphorylation of Akt. In conclusion, these results show that u-PA expression may be a potent therapeutic target in the DNE-mediated suppression of HCC invasion/migration. DNE may have potential use as a chemo-preventive agent against liver cancer metastasis.

[1]  Ying-jian Liang,et al.  GDC-0152 attenuates the malignant progression of osteosarcoma promoted by ANGPTL2 via PI3K/AKT but not p38MAPK signaling pathway. , 2015, International journal of oncology.

[2]  Jing-Gung Chung,et al.  Cantharidin impairs cell migration and invasion of A375.S2 human melanoma cells by suppressing MMP-2 and -9 through PI3K/NF-κB signaling pathways. , 2015, Anticancer research.

[3]  Mu-Kuan Chen,et al.  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 , 2014, British journal of pharmacology.

[4]  Jinyong Peng,et al.  Protective effects of the total saponins from Dioscorea nipponica Makino against carbon tetrachloride-induced liver injury in mice through suppression of apoptosis and inflammation. , 2014, International immunopharmacology.

[5]  Linlin Tang,et al.  The urokinase plasminogen activator system in breast cancer invasion and metastasis. , 2013, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[6]  Shun-Fa Yang,et al.  The Antimetastatic Effects of Resveratrol on Hepatocellular Carcinoma through the Downregulation of a Metastasis-Associated Protease by SP-1 Modulation , 2013, PloS one.

[7]  Shun-Fa Yang,et al.  Caffeic Acid Phenethyl Ester Inhibits Oral Cancer Cell Metastasis by Regulating Matrix Metalloproteinase-2 and the Mitogen-Activated Protein Kinase Pathway , 2012, Evidence-based complementary and alternative medicine : eCAM.

[8]  Shun-Fa Yang,et al.  Terminalia catappa Exerts Antimetastatic Effects on Hepatocellular Carcinoma through Transcriptional Inhibition of Matrix Metalloproteinase-9 by Modulating NF-κB and AP-1 Activity , 2012, Evidence-based complementary and alternative medicine : eCAM.

[9]  S. Chuang,et al.  Elimination of Cancer Stem-Like “Side Population” Cells in Hepatoma Cell Lines by Chinese Herbal Mixture “Tien-Hsien Liquid” , 2012, Evidence-based complementary and alternative medicine : eCAM.

[10]  K. Chow,et al.  Induction of apoptosis in human Hep3B hepatoma cells by norcantharidin through a p53 independent pathway via TRAIL/DR5 signal transduction , 2012, Chinese Journal of Integrative Medicine.

[11]  C. Schmidt,et al.  uPA and PAI-1-Related Signaling Pathways Differ between Primary Breast Cancers and Lymph Node Metastases. , 2012, Translational oncology.

[12]  J. Ko,et al.  Dioscorea nipponica Makino inhibits migration and invasion of human oral cancer HSC-3 cells by transcriptional inhibition of matrix metalloproteinase-2 through modulation of CREB and AP-1 activity. , 2012, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[13]  H. Kuo,et al.  Stromal cell‐derived factor‐1/CXC receptor 4 and β1 integrin interaction regulates urokinase‐type plasminogen activator expression in human colorectal cancer cells , 2012, Journal of cellular physiology.

[14]  Chieh-Hsi Wu,et al.  Ethanol Extracts of Fruiting Bodies of Antrodia cinnamomea Suppress CL1-5 Human Lung Adenocarcinoma Cells Migration by Inhibiting Matrix Metalloproteinase-2/9 through ERK, JNK, p38, and PI3K/Akt Signaling Pathways , 2012, Evidence-based complementary and alternative medicine : eCAM.

[15]  Jiyan Liu,et al.  Novel thienopyridine derivatives as specific anti-hepatocellular carcinoma (HCC) agents: synthesis, preliminary structure-activity relationships, and in vitro biological evaluation. , 2010, Bioorganic & medicinal chemistry letters.

[16]  J. Hong,et al.  Inhibition of bone marrow-derived dendritic cell maturation by glabridin. , 2010, International immunopharmacology.

[17]  S. Chu,et al.  Antimetastatic effects of Terminalia catappa L. on oral cancer via a down-regulation of metastasis-associated proteases. , 2010, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[18]  Joseph Irudayaraj,et al.  Biofunctionalized magnetic nanoparticle integrated mid-infrared pathogen sensor for food matrixes. , 2009, Analytical chemistry.

[19]  M. Moshi,et al.  Single-dose fluconazole versus standard 2-week therapy for oropharyngeal candidiasis in HIV-infected patients: a randomized, double-blind, double-dummy trial. , 2008, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[20]  Yun-Ching Chang,et al.  Chemoinhibitory effect of mulberry anthocyanins on melanoma metastasis involved in the Ras/PI3K pathway. , 2008, Journal of agricultural and food chemistry.

[21]  M. Francki,et al.  Quantitative trait loci for seedling and adult plant resistance to Stagonospora nodorum in wheat. , 2008, Phytopathology.

[22]  S. Chu,et al.  Antimetastatic potentials of flavones on oral cancer cell via an inhibition of matrix-degrading proteases. , 2008, Archives of oral biology.

[23]  Jianping Chen,et al.  Characterization of steroidal saponins in crude extract from Dioscorea nipponica Makino by liquid chromatography tandem multi-stage mass spectrometry. , 2007, Analytica chimica acta.

[24]  S. Chu,et al.  Silibinin inhibits cell invasion through inactivation of both PI3K-Akt and MAPK signaling pathways. , 2005, Chemico-biological interactions.

[25]  Hai-yan Wang,et al.  Chinese herbal medicine in the treatment of chronic kidney disease. , 2005, Advances in chronic kidney disease.

[26]  M. Björklund,et al.  Gelatinase-mediated migration and invasion of cancer cells. , 2005, Biochimica et biophysica acta.

[27]  R. Medcalf,et al.  Novel inhibitors of urokinase‐type plasminogen activator and matrix metalloproteinase expression in metastatic cancer cell lines , 2004, International journal of cancer.

[28]  K. Reddy,et al.  Role of MAP kinase in tumor progression and invasion , 2003, Cancer and Metastasis Reviews.

[29]  L. Tang,et al.  Antidiabetic herbal drugs officially approved in China , 2003, Phytotherapy research : PTR.

[30]  J. Parsons,et al.  Focal adhesion kinase: the first ten years , 2003, Journal of Cell Science.

[31]  Sang-Oh Yoon,et al.  Roles of matrix metalloproteinases in tumor metastasis and angiogenesis. , 2003, Journal of biochemistry and molecular biology.

[32]  Sung Hee Kim,et al.  Anti-obesity Effect of Dioscorea nipponica Makino with Lipase-inhibitory Activity in Rodents , 2003, Bioscience, biotechnology, and biochemistry.

[33]  J. Westermarck,et al.  Regulation of matrix metalloproteinase expression in tumor invasion , 1999, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[34]  L. Liotta,et al.  Tumor invasion and metastasis: an imbalance of positive and negative regulation. , 1991, Cancer research.

[35]  U. Thorgeirsson,et al.  Basement membrane type IV collagen degradation: evidence for the involvement of a proteolytic cascade independent of metalloproteinases. , 1990, Cancer research.

[36]  J. Yoshikawa,et al.  [Association of mitral valve prolapse and congenital heart disease, particularly atrial septal defect (author's transl)]. , 1976, Kokyu to junkan. Respiration & circulation.

[37]  G. Kuttan,et al.  Anti-metastatic effect of Biophytum sensitivum is exerted through its cytokine and immunomodulatory activity and its regulatory effect on the activation and nuclear translocation of transcription factors in B16F-10 melanoma cells. , 2008, Journal of experimental therapeutics & oncology.

[38]  Universidade Federal de Pernambuco/Departamento de Antibióticos do Centro de Ciências Biológicas, , 2006 .

[39]  H. Klocker,et al.  Type IV collagenase (matrix metalloproteinase-2 and -9) in prostate cancer , 2004, Prostate Cancer and Prostatic Diseases.

[40]  L. Coussens,et al.  Matrix metalloproteinases and the development of cancer. , 1996, Chemistry & biology.

[41]  O. Oke A nutrition policy for Nigeria. , 1972, World review of nutrition and dietetics.