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

51 Citations (Scopus)


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
Issue number3-4
Publication statusPublished - Mar 2012



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

ASJC Scopus subject areas

  • Food Science
  • Toxicology

Cite this