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

• Published in: Food and chemical toxicology 2012-03, Vol.50 (3-4), p.558-566
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: anti-inflammatory activity; Base Sequence; Biological and medical sciences; Cell Line, Tumor; chemoprevention; Chromatin Immunoprecipitation; Cyclic AMP Response Element-Binding Protein - metabolism; cytotoxicity; Dioscorea - chemistry; Dioscorea nipponica; DNA; DNA Primers; enzyme activity; Flow Cytometry; gelatinase A; Humans; Invasion; Matrix Metalloproteinase 2 - genetics; Matrix Metalloproteinase Inhibitors; Medical sciences; metastasis; Migration; MMP-2; mortality; mouth neoplasms; Mouth Neoplasms - enzymology; Mouth Neoplasms - pathology; neoplasm cells; Oral cancer; Otorhinolaryngology. Stomatology; Plant Extracts - pharmacology; protein synthesis; quantitative polymerase chain reaction; Real-Time Polymerase Chain Reaction; RNA; Toxicology; traditional medicine; transcription (genetics); Transcription Factor AP-1 - metabolism; Transcription, Genetic; Tumors; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology; Western blotting
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2011.12.016

► Dioscorea nipponica Makino, a popular folk medicine, exerts anti-inflammation properties. ► DNE inhibited migration/invasion capacities of human oral cancer cells, HSC-3. ► DNE inhibited matrix metalloproteinase-2 enzyme activity, and RNA and protein expression. ► DNE inhibited nuclear translocation and DNA binding activity of CREBand AP-1 on the MMP-2 promoter. ► DNE may have potential use as a chemopreventive agent against oral cancer metastasis. 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 (0–50μg/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.