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.
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.
Wan Fang Hospital, Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan.
Ming-Hsien
MH
Chien
Tsung-Ho
TH
Ying
Yih-Shou
YS
Hsieh
Yu-Chao
YC
Chang
Chia-Ming
CM
Yeh
Jiunn-Liang
JL
Ko
Wen-Sen
WS
Lee
Jer-Hua
JH
Chang
Shun-Fa
SF
Yang
D001483:Base Sequence; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D017931:DNA Primers; D027742:Dioscorea / Q000737:chemistry*; D005434:Flow Cytometry; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D061965:Matrix Metalloproteinase Inhibitors; D009062:Mouth Neoplasms / Q000201:enzymology / Q000473:pathology*; D010936:Plant Extracts / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014158:Transcription, Genetic
D017362:Cyclic AMP Response Element-Binding Protein; D017931:DNA Primers; D061965:Matrix Metalloproteinase Inhibitors; D010936:Plant Extracts; D018808:Transcription Factor AP-1; D020778:Matrix Metalloproteinase 2