Dioscorea nipponica inhibits hepatocellular carcinoma metastasis

Taiwan has high mortality and morbidity rates for hepatocellular carcinoma (HCC), the most common type of primary liver cancer. HCC is primarily caused by uncontrolled tumor metastasis. A study published in The American Journal of Chinese Medicine looked into the anti-metastasis effects of Dioscorea nipponica Makino extract (DNE) on human liver cancer cells.

• To determine the effects of DNE on the migration and invasion in HCC cells, the researchers used a wound-healing model, Boyden chamber assays, gelatin/casein zymography and Western blotting.
• The real-time PCR and promoter assays detected the transcriptional levels of matrix metalloproteinase-9 (MMP-9) and urokinase-type plasminogen activator (u-PA).
•  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 treatment.
• Furthermore, DNE treatment significantly inhibited the migration/invasion capacities of Huh7 cell lines.
• 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 that DNE inhibited u-PA expression. It also showed that the inhibitory effects were associated with the down-regulation of the transcription factors of NF-KB and SP-1 signaling pathways.
• Western blot analysis also showed that DNE inhibited PI3K and phosphorylation of Akt.

The researchers conclude that u-PA expression may be a potent therapeutic target in the DNE-mediated suppression of HCC invasion and migration. DNE may have potential use as a chemopreventive agent against liver cancer metastasis.

Journal Reference:

Hsieh MJ, Yeh CB, Chiou HL, Hsieh MC, Yang SF. DIOSCOREA NIPPONICA ATTENUATES MIGRATION AND INVASION BY INHIBITION OF UROKINASE-TYPE PLASMINOGEN ACTIVATOR THROUGH INVOLVING PI3K/AKT AND TRANSCRIPTIONAL INHIBITION OF NF-KB AND SP-1 IN HEPATOCELLULAR CARCINOMA. The American Journal of Chinese Medicine. 2016;44(01):177–195. DOI: 10.1142/s0192415x16500129