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Neobavaisoflavone sensitizes apoptosis via the inhibition of metastasis in TRAIL-resistant human glioma U373MG cells
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
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
Abstract:

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.
Keywords:Neobavaisoflavone  Apoptosis  Glioma  Metastasis  Anoikis  TRAIL
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