Curcumol induces HSC-T6 cell death through suppression of Bcl-2: Involvement of PI3K and NF-κB pathways
| Autor: | Tianjiao Xu, Bo Hong, Gang Chen, Xiaoli Wang, Meiqian Li, Yinghang Wang, Yingcai Niu |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Liver Cirrhosis
Programmed cell death Pharmaceutical Science Apoptosis Biology Cell Line chemistry.chemical_compound Annexin Hepatic Stellate Cells Animals Phosphorylation PI3K/AKT/mTOR pathway Cell Death Caspase 3 Kinase NF-kappa B NF-κB Rats Liver Proto-Oncogene Proteins c-bcl-2 chemistry Hepatic stellate cell Cancer research Phosphatidylinositol 3-Kinase Poly(ADP-ribose) Polymerases Signal transduction Sesquiterpenes Signal Transduction |
| Zdroj: | European Journal of Pharmaceutical Sciences. 65:21-28 |
| ISSN: | 0928-0987 |
| Popis: | The major feature in the molecular pathogenesis of hepatic fibrosis requires maintenance of the activated hepatic stellate cells (HSCs) phenotype by both proliferation and inhibition of apoptosis. Thus, the induction of activated HSCs apoptosis has been proposed as an antifibrotic treatment strategy. Curcumol has pro-apoptotic activity in a number of cancer cell types. The aim of this study is to test the hypothesis that the interruption of the phosphatidylinositol 3 kinase (PI3K)/nuclear factor-κB (NF-κB) signaling pathway by curcumol might induce apoptosis of activated HSCs. Our results indicated that curcumol-induced growth inhibition correlated with apoptosis induction as evidenced by Annexin V staining, and cleavage of caspase-3 and poly (ADP-ribose) polymerase (PARP) in HSC-T6. Importantly, we show that the apoptotic effect of curcumol was specific to the activated HSCs (HSC-T6). Suppression of the NF-κB translocation via inhibition of IκB-α phosphorylation by the curcumol led to the inhibition of expression of NF-κB-regulated gene, e.g. Bcl-xL and Bcl-2, in a PI3K-dependent manner, which is upstream of NF-κB activation. Also, curcumol-mediated apoptosis of HSC-T6 were reversed by LY294002 and Bay 11-7082. Taken together, our findings perfectly support the hypothesis and demonstrate that the inhibition of PI3K/NF-κB pathway by curcumol lead to HSC-T6 apoptosis. Thus, our study indicates that curcumol is a potential candidate for further preclinical study aimed at the treatment of liver fibrosis. |
| Databáze: | OpenAIRE |
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