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


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.


RESULTS
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.


CONCLUSIONS
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.
Natural Medicine Center, Korea Institute of Science and Technology, Gangneung, Gangwon-do, South Korea.
Young-Joo
YJ
Kim
Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, South Korea.
Won-Il
WI
Choi
Laboratory of Molecular Oncology, Cheil General Hospital and Women's Healthcare Center, Kwandong University College of Medicine, Seoul, South Korea.
Hyeonseok
H
Ko
Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, South Korea; Department of Pharmacology, University of Ulsan College of Medicine, Seoul, South Korea.
Youngsin
Y
So
Natural Medicine Center, Korea Institute of Science and Technology, Gangneung, Gangwon-do, South Korea.
Ki Sung
KS
Kang
Asan Institute for Medical Research, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
InKi
I
Kim
Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, South Korea.
Kunhong
K
Kim
Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, South Korea.
Ho-Geun
HG
Yoon
Department of Obstetrics and Gynecology, Cheil General Hospital and Women's Healthcare Center, Kwandong University College of Medicine, Seoul, South Korea.
Tae-Jin
TJ
Kim
Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, South Korea; Department of Pharmacology, University of Ulsan College of Medicine, Seoul, South Korea. Electronic address: choikc75@amc.seoul.kr.
Kyung-Chul
KC
Choi
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005434:Flow Cytometry; D005910:Glioma / Q000188:drug therapy / Q000473:pathology*; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D009362:Neoplasm Metastasis; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
D000970:Antineoplastic Agents; D007529:Isoflavones; D053221:TNF-Related Apoptosis-Inducing Ligand; C549830:neobavaisoflavone; D020169:Caspases
Anoikis; Apoptosis; Glioma; Metastasis; Neobavaisoflavone; TRAIL