By inhibiting snail signaling and miR-23a-3p, osthole suppresses the EMT-mediated metastatic ability in prostate cancer

Abstract

// Yu-Ching Wen 1,2 , Wei-Jiunn Lee 2 , Peng Tan 1 , Shun-Fa Yang 3,4 , Michael Hsiao 5 , Liang-Ming Lee 2 and Ming-Hsien Chien 1,6 1 Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan 2 Department of Urology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan 3 Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan 4 Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan 5 The Genomics Research Center, Academia Sinica; Taipei, Taiwan 6 Department of Education and Research, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan Correspondence to: Ming-Hsien Chien, email: // Liang-Ming Lee, email: // Keywords : prostate cancer, miR-23a-3p, snail, EMT, osthole Received : March 12, 2015 Accepted : May 13, 2015 Published : May 22, 2015 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.