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

Ming Hsien Chien, Tsung Ho Ying, Yih Shou Hsieh, Yu Chao Chang, Chia Ming Yeh, Jiunn Liang Ko, Wen Sen Lee, Jer Hua Chang, Shun Fa Yang

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Oral cancer mortality has increased during the last decade due to the difficulties in treating related metastasis. Dioscorea nipponica Makino, a popular folk medicine, exerts anti-obesity and anti-inflammation properties. However, the effect of this folk medicine on metastasis of oral cancer has yet to be fully elucidated. The present study demonstrates that D. nipponica extracts (DNE), at a range of concentrations (0-50 μg/mL), concentration-dependently inhibited migration/invasion capacities of human oral cancer cells, HSC-3, without cytotoxic effects. The anti-migration effect of DNE was also observed in two other OSCC cell lines, Ca9-22 and Cal-27. Zymography, real time PCR, and Western blotting analyses revealed that DNE inhibited matrix metalloproteinase-2 (MMP-2) enzyme activity, and RNA and protein expression. The inhibitory effects of DNE on MMP-2 proceeded by up-regulating tissue inhibitor of metalloproteinase-2 (TIMP-2), as well as suppressing nuclear translocation and DNA binding activity of cAMP response element-binding (CREB) and activating protein-1 (AP-1) on the MMP-2 promoter in HSC-3 cells. In conclusion, DNE inhibited the invasion of oral cancer cells and may have potential use as a chemopreventive agent against oral cancer metastasis.

Original languageEnglish
Pages (from-to)558-566
Number of pages9
JournalFood and Chemical Toxicology
Volume50
Issue number3-4
DOIs
Publication statusPublished - Mar 2012

Fingerprint

Dioscorea nipponica
Dioscorea
Cyclic AMP Response Element-Binding Protein
gelatinase A
response elements
Mouth Neoplasms
Matrix Metalloproteinase 2
Response Elements
Cells
Modulation
Medicine
metastasis
extracts
Traditional Medicine
Tissue Inhibitor of Metalloproteinase-2
Neoplasm Metastasis
Proteins
proteins
Enzyme activity
cells

Keywords

  • Dioscorea nipponica
  • Invasion
  • Migration
  • MMP-2
  • Oral cancer

ASJC Scopus subject areas

  • Food Science
  • Toxicology

Cite this

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. / Chien, Ming Hsien; Ying, Tsung Ho; Hsieh, Yih Shou; Chang, Yu Chao; Yeh, Chia Ming; Ko, Jiunn Liang; Lee, Wen Sen; Chang, Jer Hua; Yang, Shun Fa.

In: Food and Chemical Toxicology, Vol. 50, No. 3-4, 03.2012, p. 558-566.

Research output: Contribution to journalArticle

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abstract = "Oral cancer mortality has increased during the last decade due to the difficulties in treating related metastasis. Dioscorea nipponica Makino, a popular folk medicine, exerts anti-obesity and anti-inflammation properties. However, the effect of this folk medicine on metastasis of oral cancer has yet to be fully elucidated. The present study demonstrates that D. nipponica extracts (DNE), at a range of concentrations (0-50 μg/mL), concentration-dependently inhibited migration/invasion capacities of human oral cancer cells, HSC-3, without cytotoxic effects. The anti-migration effect of DNE was also observed in two other OSCC cell lines, Ca9-22 and Cal-27. Zymography, real time PCR, and Western blotting analyses revealed that DNE inhibited matrix metalloproteinase-2 (MMP-2) enzyme activity, and RNA and protein expression. The inhibitory effects of DNE on MMP-2 proceeded by up-regulating tissue inhibitor of metalloproteinase-2 (TIMP-2), as well as suppressing nuclear translocation and DNA binding activity of cAMP response element-binding (CREB) and activating protein-1 (AP-1) on the MMP-2 promoter in HSC-3 cells. In conclusion, DNE inhibited the invasion of oral cancer cells and may have potential use as a chemopreventive agent against oral cancer metastasis.",
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