6-Gingerol Prevents Disassembly of Cell Junctions and Activities of MMPs in Invasive Human Pancreas Cancer Cells through ERK-NF-κB-Snail Signal Transduction PathwayReport as inadecuate




6-Gingerol Prevents Disassembly of Cell Junctions and Activities of MMPs in Invasive Human Pancreas Cancer Cells through ERK-NF-κB-Snail Signal Transduction Pathway - Download this document for free, or read online. Document in PDF available to download.

Evidence-Based Complementary and Alternative MedicineVolume 2013 2013, Article ID 761852, 9 pages

Research ArticleDepartment of Herbal Pharmacology, College of Oriental Medicine, Daegu Haany University, 165 Sang Dong, Suseong gu, Daegu 706-828, Republic of Korea

Received 24 May 2013; Revised 15 July 2013; Accepted 14 August 2013

Academic Editor: Dan-Ning Hu

Copyright © 2013 Sung Ok Kim and Mi Ryeo Kim. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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-κB 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-κB-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-κB activity. In conclusion, these findings demonstrate that 6-gingerol regulates TJ-related proteins and suppresses invasion and metastasis through NF-κB-Snail inhibition via inhibition of the ERK pathway. Therefore, 6-gingerol may suppress the invasive activity of PANC-1 cells.





Author: Sung Ok Kim and Mi Ryeo Kim

Source: https://www.hindawi.com/



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