Morin Inhibits Proliferation, Migration, and Invasion of Bladder Cancer EJ Cells via Modulation of Signaling Pathways, Cell Cycle Regulators, and Transcription Factor-Mediated MMP-9 Expression.
Preclinical Research Previous studies have shown that morin exerts diverse pharmacological activities. In this study, we investigated the inhibitory activity of morin on bladder cancer EJ cells. Morin significantly inhibited EJ cell proliferation, which was related to the G1-phase cell cycle arrest together with the reduced expression of cyclin D1, cyclin E, CDK2, and CDK4 via increased expression of p21WAF1. Morin also increased ERK1/2 phosphorylation and decreased JNK and AKT phosphorylation without altering the p38MAPK phosphorylation levels. Morin treatment suppressed the migration and invasion of EJ cells in wound-healing and transwell cell invasion assays. Zymographic and electrophoretic mobility shift assays showed that morin suppressed the expression of matrix metalloproteinase-9 (MMP-9) via repression of the binding activity of AP-1, Sp-1, and NF-κB. Collectively, these results demonstrate that morin reduced cyclin D1, cyclin E, CDK2 and CDK4 expression via the induction of p21WAF1 expression, increased ERK1/2 phosphorylation and decreased JNK, and AKT phosphorylation, and prevented MMP-9 expression via the inhibition of transcription factors AP-1, Sp-1, and NF-κB, thereby resulting in the inhibition of growth, migration, and invasion of bladder cancer EJ cells. These results provide a novel insight into the use of morin in the prevention of bladder cancer. Drug Dev Res 78 : 81-90, 2017. © 2017 Wiley Periodicals, Inc.
Department of Food Science and Nutrition, Jeju National University, Jeju, 63243, South Korea.
Seung-Shick
SS
Shin
Department of Food and Nutrition, Chung-Ang University, Anseong, 17546, South Korea.
Se Yeon
SY
Won
Department of Food and Nutrition, Chung-Ang University, Anseong, 17546, South Korea.
Dae-Hwa
DH
Noh
Department of Food and Nutrition, Chung-Ang University, Anseong, 17546, South Korea.
Byungdoo
B
Hwang
Department of Urology, Chungbuk National University, Cheongju, Chungbuk, 361-763, South Korea.
Wun-Jae
WJ
Kim
Department of Food and Nutrition, Chung-Ang University, Anseong, 17546, South Korea.
Sung-Kwon
0000-0002-4514-3457
SK
Moon
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology* / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D015398:Signal Transduction / Q000187:drug effects; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D047309:Flavones
D000970:Antineoplastic Agents; D005419:Flavonoids; D020780:Matrix Metalloproteinase 9; C008548:morin; D047309:Flavones; C579270:MMP9 protein, human
bladder cancer; invasion; migration; morin; proliferation