Abstract
Here we showed that Osthole, 7-methoxy-8-(3-methyl-2-butenyl) coumarin, a bioactive coumarin derivative extracted from medicinal plants, inhibited migration, invasion, epithelial to mesenchymal transition (EMT) in androgen-independent prostate cancer (AIPC) cells in vitro and metastasis of AIPC in vivo. In patients, high Snail levels were correlated with a higher histological Gleason sum and poor survival rates. Osthole inhibited the TGF-β/Akt/MAPK pathways, reduced Snail-DNA-binding activity and induced E-cadherin. We found that osthole decreased miR-23a-3p. Ectopic miR-23a-3p suppressed E-cadherin 3' untranslated region reporter activity and E-cadherin expression, and relieved the motility suppression caused by osthole treatment.
Keywords:
EMT; miR-23a-3p; osthole; prostate cancer; snail.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3' Untranslated Regions
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Animals
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Cadherins / metabolism
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Cell Line, Tumor
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Cell Movement
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Cell Proliferation
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Cell Survival
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Coumarins / chemistry*
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Disease Progression
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Down-Regulation
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Epithelial-Mesenchymal Transition / drug effects*
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Gene Expression Regulation, Neoplastic
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Genes, Reporter
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Humans
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Male
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Mice
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Mice, SCID
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MicroRNAs / antagonists & inhibitors
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MicroRNAs / metabolism*
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Neoplasm Metastasis
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Neoplasm Transplantation
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Prostatic Neoplasms / drug therapy
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Prostatic Neoplasms / metabolism*
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Prostatic Neoplasms / pathology
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Signal Transduction*
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Snail Family Transcription Factors
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Transcription Factors / antagonists & inhibitors
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Transcription Factors / metabolism*
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Wound Healing
Substances
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3' Untranslated Regions
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Cadherins
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Coumarins
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MIRN23a microRNA, human
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MicroRNAs
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Snail Family Transcription Factors
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Transcription Factors
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osthol