Curcumin activates Wnt/β-catenin signaling pathway through inhibiting the activity of GSK-3β in APPswe transfected SY5Y cells.

Wnt/β-catenin signaling pathway plays an important role in the genesis and development of Alzheimer's disease. The study aims to investigate the effect of Curcumin on the expression of GSK-3β, β-catenin and CyclinD1 in vitro, which are tightly correlated with Wnt/β-catenin signaling pathway, and also to explore the mechanisms, which will provide a novel therapeutic intervention for treatment of Alzheimer's disease. Plasmid APPswe and BACE1-mychis were transiently co-transfected into SHSY5Y cells by Liposfectamin™2000. The cells were treated with Curcumin at 0, 1.25, 5.0, 20.0 μmol/L for 24 h, or with Curcumin at 5.0 μmol/L for 0, and 12, 24 and 48 h for time course assay. Cell lysates were collected for RT-PCR, Western blot assay and immunofluorescent staining were carried out for detecting the effect of Curcumin on the expression of GSK-3β, β-catenin and CyclinD1. RT-PCR and Western blot results showed that the expression of GSK-3β mRNA and protein significantly decreased in the transfected cells treated with Curcumin, and that the changes were in a dose and time-dependent manner (P<0.05); however, the protein expression of GSK-3β-Ser9 was increased (P<0.05). Meanwhile, the expressions of β-catenin and transcriptional factors CyclinD1 mRNA and protein increased and the changes were also in a dose and time-dependent manner (P<0.05). Immunofluorescent staining results not only confirmed the above changes, but also showed that β-catenin had translocated into the nucleus gradually with the increased dosage of Curcumin. Therefore, GSK-3β is a potential target for treatment of AD. Curcumin could activate the Wnt/β-catenin signaling pathway through inhibiting the expression of GSK-3β and inducing the expression of β-catenin and CyclinD1, which will provide a new theory for treatment of neurodegenerative diseases by Curcumin.

Zhang X ，Yin WK ，Shi XD ，Li Y ... -  《-》

MicroRNA-26b inhibits cell proliferation and cytokine secretion in human RASF cells via the Wnt/GSK-3β/β-catenin pathway.

Sun J ，Yan P ，Chen Y ，Chen Y ，Yang J ，Xu G ，Mao H ，Qiu Y ... -  《Diagnostic Pathology》

Curcumin mediates presenilin-1 activity to reduce β-amyloid production in a model of Alzheimer's Disease.

Xiong Z ，Hongmei Z ，Lu S ，Yu L ... -  《-》

GSK-3β suppresses the proliferation of rat hepatic oval cells through modulating Wnt/β-catenin signaling pathway.

Ji XK ，Xie YK ，Zhong JQ ，Xu QG ，Zeng QQ ，Wang Y ，Zhang QY ，Shan YF ... -  《-》

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

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. 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. 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. 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.

Eren D ，Betul YM 《-》