Quercetin-6-C-β-d-glucopyranoside, natural analog of quercetin exhibits anti-prostate cancer activity by inhibiting Akt-mTOR pathway via aryl hydrocarbon receptor
| Autor: | Rajeev Kumar, E. Ramakrishna, Rakesh Maurya, Hamidullah, Naibedya Chattopadhyay, Karan Singh Saini, Sudhir Kumar, Rituraj Konwar, Amit Kumar |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Cell cycle checkpoint Cell Survival Apoptosis Caspase 3 Pharmacology Ligands Resting Phase Cell Cycle Biochemistry Cell Line Glucosides Cell Line Tumor Basic Helix-Loop-Helix Transcription Factors Humans Cytotoxic T cell Protein kinase B PI3K/AKT/mTOR pathway Binding Sites biology TOR Serine-Threonine Kinases Prostate General Medicine Cell cycle Aryl hydrocarbon receptor Antineoplastic Agents Phytogenic Neoplasm Proteins Molecular Docking Simulation Prostatic Neoplasms Castration-Resistant Receptors Aryl Hydrocarbon Structural Homology Protein biology.protein Quercetin RNA Interference Reactive Oxygen Species Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | Biochimie. 119:68-79 |
| ISSN: | 0300-9084 |
| DOI: | 10.1016/j.biochi.2015.10.012 |
| Popis: | Pre-clinical studies suggest mitigating effect of dietary flavonoid quercetin against cancer and other diseases. However, quercetin suffers from poor metabolic stability, which appears to offset its pharmacological efficacy. Recently, we isolated quercetin-6-C-β-D-glucopyranoside (QCG) from Ulmus wallichiana planchon that has greater stability profile over quercetin. In the present study, the cytotoxic and apoptotic effects of QCG on prostate cancer cells were assessed. QCG inhibited prostate cancer cell proliferation by arresting cells at G0/G1 phase of cell cycle and induces apoptosis as evident from cytochrome c release, cleavage of caspase 3 and poly (ADP-ribose) polymerase. Mechanistic studies revealed that QCG inhibited reactive oxygen species (ROS) generation and Akt/mTOR cell survival pathways. Aryl hydrocarbon receptor (AhR) was a critical mediator of QCG action as knockdown of AhR attenuated QCG-induced cell cycle arrest, apoptosis and inhibition of Akt/mTOR pathway in prostate cancer cells. Taken together, our results suggest that QCG exhibits anti-cancer activity against prostate cancer cells via AhR-mediated down regulation of Akt/mTOR pathway in PC-3 cells. |
| Databáze: | OpenAIRE |
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