ABSTRACT
TRAIL can induce apoptosis in some cancer cells and is an immune effector in the surveillance and elimination of developing tumors. Yes, some cancers are resistant to TRAIL. Delphinidin, a polyphenolic compound contained in brightly colored fruits and vegetables, has anti-inflammatory, anti-oxidant, and anti-tumorigenic activities. Here we showed that delphinidin sensitized TRAIL-resistant human prostate cancer cells to undergo apoptosis. Cells treated with delphinidin and TRAIL activated the extrinsic and intrinsic pathways of caspase activation. TRAIL-induced apoptosis in prostate cancer cells pretreated with delphinidin was dependent on death receptor 5 (DR5) and downstream cleavage of histone deacetylase 3 (HDAC3). In conclusion, delphinidin sensitizes prostate cancer cells to TRAIL-induced apoptosis by inducing DR5, thus causing caspase-mediated HDAC3 cleavage. Our data reveal a potential way of chemoprevention of prostate cancer by enabling TRAIL-mediated apoptosis.
Subject(s)
Anthocyanins/pharmacology , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Histone Deacetylases/metabolism , Prostatic Neoplasms/drug therapy , Receptors, TNF-Related Apoptosis-Inducing Ligand/biosynthesis , TNF-Related Apoptosis-Inducing Ligand/pharmacology , Anthocyanins/administration & dosage , Apoptosis/drug effects , Caspases/metabolism , Cell Line, Tumor , Drug Synergism , Humans , Male , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathology , Receptors, TNF-Related Apoptosis-Inducing Ligand/metabolism , TNF-Related Apoptosis-Inducing Ligand/administration & dosage , TransfectionABSTRACT
AIMS: Neobavaisoflavone (NBIF), an isoflavone isolated from Psoralea corylifolia (Leguminosae), has striking anti-inflammatory and anti-cancer effects. NBIF inhibits the proliferation of prostate cancer in vitro and in vivo. MAIN METHODS: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a key endogenous molecule that selectively induces apoptosis in cancer cells with little or no toxicity in normal cells. However, some cancer cells, including U373MG cells, are resistant to TRAIL-mediated apoptosis. We demonstrated that the cell viability, migration and invasion assay were used in U373MG glioma cells. KEY FINDINGS: In this study, we found that NBIF sensitizes human U373MG glioma cells to TRAIL-mediated apoptosis. Co-treatment of TRAIL and NBIF effectively induced Bid cleavage and activated caspases 3, 8, and 9. Importantly, DR5 expression was upregulated by NBIF. We also observed that the combination NBIF and TRAIL increased expression of BAX. We further demonstrate that NBIF induced TRAIL-mediated apoptosis in human glioma cells by suppressing migration and invasion, and by inhibiting anoikis resistance. SIGNIFICANCE: Taken together, our results suggest that NBIF reduces the resistance of cancer cells to TRAIL and that the combination of NBIF and TRAIL may be a new therapeutic strategy for treating TRAIL-resistant glioma cells.
Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Glioma/pathology , Isoflavones/pharmacology , TNF-Related Apoptosis-Inducing Ligand/pharmacology , Blotting, Western , Caspases/genetics , Caspases/metabolism , Cell Line, Tumor , Cell Proliferation/drug effects , Flow Cytometry , Glioma/drug therapy , Humans , Neoplasm Metastasis , Up-Regulation/drug effectsABSTRACT
Transforming growth factor-ß1, the key ligand of Smad-dependent signaling pathway, is critical for epithelial-mesenchymal transition during embryo-morphogenesis, fibrotic diseases, and tumor metastasis. In this study, we found that activation of p300/CBP, a histone acetyltransferase, by TGF-ß1 mediates Epithelial-mesenchymal transition (EMT) via acetylating Smad2 and Smad3 in TGF-ß1 signaling pathway. We demonstrated that treatment with EGCG inhibited p300/CBP activity in human lung cancer cells. Also, we observed that EGCG potently inhibited TGF-ß1-induced EMT and reversed the up-regulation of various genes during EMT. Our findings suggest that EGCG inhibits the induction of p300/CBP activity by TGF-ß1. Therefore, EGCG inhibits TGF-ß1-mediated EMT by suppressing the acetylation of Smad2 and Smad3 in human lung cancer cells.
