title: Revealing the effect of 6-gingerol, 6-shogaol and curcumin on mPGES-1, GSK-3β and β-catenin pathway in A549 cell line.
abstract: OBJECTIVE
  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 E2 synthase 1 (mPGES-1) which is related with cancer progression and inflammation as well as β-catenin and glycogen synthase kinase 3β (GSK-3β) that are the main components of Wnt/GSK3 pathway. As it is known activation of GSK-3β 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 GSK3β pathway. IL-1β 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.
  
  
  METHODS
  A549 cells were incubated with interleukin 1β (IL-1β) for 24 h in order to maintain mPGES-1 enzyme induction. Experiments were performed both on IL-1β and non-IL-1β group. Real time cell analysis was performed to determine the cytotoxicity. Samples for western blotting and RT-PCR were collected after 24 h incubation with compounds to determine the amount of mPGES-1, GSK-3β, p-GSK-3β, β-catenin protein and mRNA. PGE2 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-1β proliferate faster than non-IL-1β ones. This shows that induced mPGES-1 might play a role through GSK3β pathway and 24 h IC50 value of 6-shogaol is 62 μM. IL-1β increased protein and mRNA levels of mPGES-1, p-GSK-3β, β-catenin and GSK-3β in control group. Effects of curcumin and 6-shogaol on these parameters were against IL-1β's effect while 6-gingerol was not effective at all. Furthermore, 6-shogaol and curcumin might be effective on GSK3β pathway via lowering PGE2 levels.
  
  
  CONCLUSIONS
  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 GSK3β pathway. May be these results might used for designing in vivo studies in future.
authors.affiliation: Erciyes University, Faculty of Pharmacy, Department of Pharmacology, Kayseri, Turkey. Electronic address: erendemirpolat@yahoo.com.
authors.forename: Demirpolat
authors.initials: D
authors.lastname: Eren
authors.affiliation: Erciyes University, Faculty of Pharmacy, Department of Pharmacology, Kayseri, Turkey. Electronic address: eczbetul@yahoo.com.
authors.forename: Yerer Mukerrem
authors.initials: YM
authors.lastname: Betul
mesh_terms: D000072283:A549 Cells; D015153:Blotting, Western; D002396:Catechols / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000737:chemistry / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D005233:Fatty Alcohols / Q000737:chemistry / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D000071679:Glycogen Synthase Kinase 3 beta / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D008954:Models, Biological; D000071876:Prostaglandin-E Synthases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D002396:Catechols; D005233:Fatty Alcohols; D053583:Interleukin-1beta; D012333:RNA, Messenger; D051176:beta Catenin; C040115:shogaol; C007845:gingerol; D000071679:Glycogen Synthase Kinase 3 beta; C000605862:PTGES protein, human; D000071876:Prostaglandin-E Synthases; D003474:Curcumin; D015232:Dinoprostone
keywords: 6-Gingerol; 6-Shogaol; A549; GSK-3β; mPGES-1; β-Catenin