Diosgenin suppresses hepatocyte growth factor (HGF)-induced epithelial-mesenchymal transition by down-regulation of Mdm2 and vimentin

Hsiang Yu Chang, Ming Ching Kao, Tzong Der Way, Chi-Tang Ho, Earl Fu

Research output: Contribution to journalArticle

29 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)5357-5363
Number of pages7
JournalJournal of agricultural and food chemistry
Volume59
Issue number10
DOIs
StatePublished - May 25 2011

Fingerprint

Diosgenin
diosgenin
hepatocyte growth factor
Epithelial-Mesenchymal Transition
Hepatocyte Growth Factor
vimentin
Vimentin
Down-Regulation
Prostatic Neoplasms
prostatic neoplasms
Cells
Scattering
Phosphorylation
phosphatidylinositol 3-kinase
colorectal neoplasms
Phosphatidylinositol 3-Kinases
Colorectal Neoplasms
phosphorylation
phosphotransferases (kinases)
Phosphotransferases

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Agricultural and Biological Sciences(all)

Keywords

  • Akt
  • C-Met
  • Diosgenin
  • Epithelial-mesenchymal transition
  • Mdm2

Cite this

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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.",
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Diosgenin suppresses hepatocyte growth factor (HGF)-induced epithelial-mesenchymal transition by down-regulation of Mdm2 and vimentin. / Chang, Hsiang Yu; Kao, Ming Ching; Way, Tzong Der; Ho, Chi-Tang; Fu, Earl.

In: Journal of agricultural and food chemistry, Vol. 59, No. 10, 25.05.2011, p. 5357-5363.

Research output: Contribution to journalArticle

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AU - Chang, Hsiang Yu

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AU - Way, Tzong Der

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AU - Fu, Earl

PY - 2011/5/25

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AB - 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.

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