Neobavaisoflavone sensitizes apoptosis via the inhibition of metastasis in TRAIL-resistant human glioma U373MG cells |
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Authors: | Young-Joo Kim Won-Il Choi Hyeonseok Ko Youngsin So Ki Sung Kang InKi Kim Kunhong Kim Ho-Geun Yoon Tae-Jin Kim Kyung-Chul Choi |
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Institution: | 1. Natural Medicine Center, Korea Institute of Science and Technology, Gangneung, Gangwon-do, South Korea;2. Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, South Korea;3. Department of Pharmacology, University of Ulsan College of Medicine, Seoul, South Korea;4. Department of Obstetrics and Gynecology, Cheil General Hospital and Women''s Healthcare Center, Kwandong University College of Medicine, Seoul, South Korea;5. Laboratory of Molecular Oncology, Cheil General Hospital and Women''s Healthcare Center, Kwandong University College of Medicine, Seoul, South Korea;6. Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, South Korea;g Asan Institute for Medical Research, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea |
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Abstract: | AimsNeobavaisoflavone (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 methodsTumor 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 findingsIn 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.SignificanceTaken 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. |
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Keywords: | Neobavaisoflavone Apoptosis Glioma Metastasis Anoikis TRAIL |
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