title: Diosgenin suppresses hepatocyte growth factor (HGF)-induced epithelial-mesenchymal transition by down-regulation of Mdm2 and vimentin.
abstract: Substantial activation of the hepatocyte growth factor (HGF)/c-Met pathway leads to cancer cell scattering and invasion and has been observed in several types of cancers, including prostate and colorectal cancers. The phosphorylation cascade downstream of HGF, particularly PI3K/Akt signaling, regulates epithelial-to-mesenchymal transition (EMT). How this signaling governs EMT and whether specific kinases respond to particular EMT effectors remain unclear. This study found specific increases in Mdm2 and vimentin rather than the coregulation of an array of EMT marker proteins in response to HGF-induced EMT in DU145 prostate cancer cells. Importantly, it was further found that diosgenin abrogated HGF-induced DU145 cell scattering and invasion. Moreover, diosgenin effectively inhibited the HGF-induced increases in Mdm2 and vimentin by down-regulating phosphorylated Akt and mTOR. In summary, the results suggest that diosgenin may be a potential compound for use in prostate cancer therapy to target the major HGF-induced EMT pathway.
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center and Academia Sinica, Taipei, Taiwan.
authors.forename: Hsiang-Yu
authors.initials: HY
authors.lastname: Chang
authors.forename: Ming-Ching
authors.initials: MC
authors.lastname: Kao
authors.forename: Tzong-Der
authors.initials: TD
authors.lastname: Way
authors.forename: Chi-Tang
authors.initials: CT
authors.lastname: Ho
authors.forename: Earl
authors.initials: E
authors.lastname: Fu
mesh_terms: D004144:Diosgenin / Q000494:pharmacology*; D004848:Epithelium / Q000473:pathology*; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008648:Mesoderm / Q000473:pathology*; D009361:Neoplasm Invasiveness; D010766:Phosphorylation / Q000502:physiology; D011471:Prostatic Neoplasms / Q000473:pathology / Q000517:prevention & control; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014746:Vimentin / Q000235:genetics / Q000502:physiology*
chemical_list: D014746:Vimentin; D017228:Hepatocyte Growth Factor; D051736:Proto-Oncogene Proteins c-mdm2; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D004144:Diosgenin