Revealing the effect of 6-gingerol, 6-shogaol and curcumin on mPGES-1, GSK-3β and β-catenin pathway in A549 cell line

Background and aim: In our study, anticancer effects of 6-gingerol, 6-shogaol from ginger and curcumin from turmeric were investigated and the results were compared with each other. We aimed to reveal their effects on microsomal prostaglandine E-2 synthase 1 (mPGES-1) which is related with cancer progression and inflammation as well as beta-catenin and glycogen synthase kinase 3 beta (GSK-3 beta) that are the main components of Wnt/GSK3 pathway. As it is known activation of GSK-3 beta and high levels of mPGES-1 pathway leads to cell proliferation and aggravates cancer progression. Therefore both of them are potential targets for cancer therapy. 6-shogaol and 6-gingerol' s effect on this pathway is not known very well up to now while curcumin that is known as an mPGES-1 inhibitor has anticancer properties via this pathway and many other pathways. Besides being in Zingiberaceae family, ginger's 6-gingerol and 6-shogaol have a molecular similarity with turmeric's curcumin. In our study we investigated their effects using a popular non small lung cancer cell line named A549 which expresses mPGES-1 and has active GSK3 beta pathway. IL-1 beta was used for inducing mPGES-1 and enabling the cancer characteristics such as cell proliferation. So compounds that inactivates or decreases the level of these components might be potential anticancer agents. Materials and methods: A549 cells were incubated with interleukin 1 beta (IL-1 beta) for 24 h in order to maintain mPGES-1 enzyme induction. Experiments were performed both on IL-1 beta and non-IL-1 beta group. Real time cell analysis was performed to determine the cytotoxicity. Samples for western blotting and RTPCR were collected after 24 h incubation with compounds to determine the amount of mPGES-1, GSK-3 beta, p-GSK-3 beta, beta-catenin protein and mRNA. PGE(2) which is the end product of mPGES-1 was measured by using ELISA kit. Results: As a result of cell profile assay, cells exposed to IL-1 beta proliferate faster than non-IL-1 beta ones. This shows that induced mPGES-1 might play a role through GSK3 beta pathway and 24 h IC50 value of 6-shogaol is 62 mu M. IL-1 beta increased protein and mRNA levels of mPGES-1, p-GSK-3 beta, beta-catenin and GSK-3 beta in control group. Effects of curcumin and 6-shogaol on these parameters were against IL-1 beta's effect while 6-gingerol was not effective at all. Furthermore, 6-shogaol and curcumin might be effective on GSK3 beta pathway via lowering PGE(2) levels. Conclusion: We saw that 6-shogaol is as effective as curcumin on this pathway and our study shows that 6-shogaol might show its anticancer properties via mPGES-1 and GSK3 beta pathway. May be these results might used for designing in vivo studies in future. (C) 2016 Elsevier Ireland Ltd. All rights reserved.