To study the effects of [6]-
gingerol, a ginger
phytochemical, on tight junction (TJ) molecules, we investigated TJ tightening and signal transduction pathways in human pancreatic duct cell-derived
cancer cell line PANC-1. The following methods were utilized: MTT assay to determine cytotoxicity; zymography to examine
matrix metalloproteinase (
MMP) activities; transepithelial electrical resistance (TER) and paracellular flux for TJ measurement; RT-PCR and immunoblotting for
proteins related to TJ and invasion; and EMSA for NF- κ B activity in PANC-1 cells. Results revealed that TER significantly increased and
claudin 4 and MMP-9 decreased compared to those of the control. TJ
protein levels, including zonula occludens (ZO-) 1,
occludin, and
E-cadherin, increased in [6]-
gingerol-treated cells, which correlated with a decrease in paracellular flux and
MMP activity. Furthermore, NF- κ B/Snail nuclear translocation was suppressed via downregulation of the
extracellular signal-regulated kinase (ERK) pathway in response to [6]-
gingerol treatment. Moreover, treatment with
U0126, an ERK inhibitor, completely blocked NF- κ B activity. In conclusion, these findings demonstrate that [6]-
gingerol regulates TJ-related
proteins and suppresses invasion and
metastasis through NF- κ B/Snail inhibition via inhibition of the ERK pathway. Therefore, [6]-
gingerol may suppress the invasive activity of PANC-1 cells.