1. Galangin inhibits the cell progression and induces cell apoptosis through activating PTEN and Caspase-3 pathways in retinoblastoma.
- Author
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Zou WW and Xu SP
- Subjects
- Animals, Caspase 3 metabolism, Cell Line, Tumor, Cell Movement drug effects, Cell Proliferation drug effects, Flow Cytometry, Gene Expression Regulation, Neoplastic, Gene Knockdown Techniques, Humans, Male, Mice, Mice, Nude, PTEN Phosphohydrolase genetics, Retinoblastoma pathology, Xenograft Model Antitumor Assays, Antineoplastic Agents, Phytogenic pharmacology, Apoptosis drug effects, Flavonoids pharmacology, Retinoblastoma drug therapy
- Abstract
Retinoblastoma is reported as a rare cancer that occurs during childhood. Although several treatments are available for retinoblastoma, there is a need for alternative new treatment modalities for retinoblastoma with better safety and efficacy profile. Galangin (3,5,7-trihydroxyflavone), is a flavonoid compound, which is found in high concentration in lesser galangal. Galangin has been reported to have various bioactivities, including anti-inflammation, anti-oxidative stress and anti-cancer through various pathways. The objective of our study was to explore the effects of galangin on the suppression of retinoblastoma in vitro and in vivo. Using MTT analysis, transwell-chamber migration analysis, colony-forming analysis, wound healing analysis, immunofluorescent assay of KI-67, we found that galangin exhibited a suppressive effect on human retinoblastoma cell proliferation and migration. Moreover, PTEN, a tumor-suppressor, was increased by galangin in cancer cells and in tumor tissues isolated from retinoblastoma xenograft models. Additionally, galangin reduced protein kinase B (Akt) phosphorylation, which was associated with PTEN up-regulation. Galangin-reduced Akt activation and cell proliferation was abolished by PTEN knockdown, which might be associated with the over-expression of phosphatidylinositol-3,4,5-triphosphate (PIP3)/diphosphate product (PIP2). Furthermore, flow cytometry, Hoechst 33258 staining and western blot assays indicated that galangin could induce apoptosis through promoting Caspase-3 pathway, which was, at least partly, dependent on PTEN expression. Our data illustrated that galangin treatment suppressed the growth of retinoblastoma tumor in vivo by anti-proliferative and apoptogenic mechanisms. Thus, galangin might be a safe and promising non-chemotherapeutic drug, which could be useful as an adjuvant against retinoblastoma., (Copyright © 2017. Published by Elsevier Masson SAS.)
- Published
- 2018
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