Eupafolin suppresses prostate cancer by targeting phosphatidylinositol 3-kinase-mediated Akt signaling

Kangdong Liu, Chanmi Park, Hanyong Chen, Joonsung Hwang, N. R. Thimmegowda, Eun Young Bae, Ki Won Lee, Hong Gyum Kim, Haidan Liu, Nak Kyun Soung, Cong Peng, Jae Hyuk Jang, Kyoon Eon Kim, Jong Seog Ahn, Ann M. Bode, Ziming Dong, Bo Yeon Kim, Zigang Dong

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Phosphatase and tensin homolog (PTEN) loss or mutation consistently activates the phosphatidylinositol 3-kinase (PI3-K)/Akt signaling pathway, which contributes to the progression and invasiveness of prostate cancer. Furthermore, the PTEN/PI3-K/Akt and Ras/MAPK pathways cooperate to promote the epithelial-mesenchymal transition (EMT) and metastasis initiated from prostate stem/progenitor cells. For these reasons, the PTEN/PI3-K/Akt pathway is considered as an attractive target for both chemoprevention and chemotherapy. Herein we report that eupafolin, a natural compound found in common sage, inhibited proliferation of prostate cancer cells. Protein content analysis indicated that phosphorylation of Akt and its downstream kinases was inhibited by eupafolin treatment. Pull-down assay and in vitro kinase assay results indicated that eupafolin could bind with PI3-K and attenuate its kinase activity. Eupafolin also exhibited tumor suppressive effects in vivo in an athymic nude mouse model. Overall, these results suggested that eupafolin exerts antitumor effects by targeting PI3-K.

Original languageEnglish (US)
Pages (from-to)751-760
Number of pages10
JournalMolecular Carcinogenesis
Volume54
Issue number9
DOIs
StatePublished - Sep 1 2015

Keywords

  • Akt
  • Chemoprevention
  • Eupafolin
  • Phosphatidylinositol 3-kinase
  • Prostate cancer

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