Exp Ther Med. 2019 Oct ;18(4):2825-2832. Epub 2019 Aug 14. PMID: 31572529
Eckol inhibits Reg3A-induced proliferation of human SW1990 pancreatic cancer cells.
Pancreatic cancer (PaC) is characterized by a highly inflammatory tumor microenvironment, and inflammatory mediators are implicated in the progression of this cancer. Regenerating gene protein (Reg) 3A is significantly upregulated during pancreatic inflammation, and has been demonstrated to serve an important role during PaC progression, based on its increased expression levels in PaC and potent cell proliferation-promoting activity. The aim of the present study was to investigate the effect of eckol, a phlorotannin compound with a variety of biological activities including anti-inflammatory, anti-tumor and cytoprotective effects, on Reg3A-induced proliferation of human SW1990 PaC cells. SW1990 cells were pre-treated with eckol for 48 h at concentrations of 5, 10 and 20µg/ml. Subsequently, Reg3A protein was added to the culture media at a final concentration of 50 ng/ml in the presence or absence of eckol for 24 h. The cytotoxicity and proliferative capacity of the SW1990 cells was determined using an MTT and flow cytometry analysis. Cell colony formation was also used to determine the effect of eckol on the anchorage-independent growth and colony-forming capacity of Reg3A-treated PaC cells. The expression levels of cyclin D1, STAT3, JAK2, and NF-κB p65 were measured with reverse transcription-quantitative PCR and western blotting. Eckol reduced Reg3A-promoted cell survival, inhibited Reg3A-induced cell cycle progression and inhibited colony growth of SW1990 cells in soft agar in a concentration-dependent manner. Additionally, the Reg3A-mediated upregulation of expression of JAK2, STAT3, NF-κBp65 and cyclin D1 was reduced when treated with eckol. Reg3A is upregulated during pancreatic inflammation and exhibits a pro-growth function and may thus serve a critical role during inflammation-driven PaC malignancies. Eckol may be a potential protective agent against progression of PaC accompanied by pancreatic inflammation.