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

• Published in: Molecular carcinogenesis Vol. 54; no. 9; pp. 751 - 760
• Main Authors: Liu, Kangdong, Park, Chanmi, Chen, Hanyong, Hwang, Joonsung, Thimmegowda, N.R., Bae, Eun Young, Lee, Ki Won, Kim, Hong-Gyum, Liu, Haidan, Soung, Nak Kyun, Peng, Cong, Jang, Jae Hyuk, Kim, Kyoon Eon, Ahn, Jong Seog, Bode, Ann M., Dong, Ziming, Kim, Bo Yeon, Dong, Zigang
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.09.2015; Wiley Subscription Services, Inc
• Subjects: Akt; Animals; Antineoplastic Agents, Phytogenic - therapeutic use; Cancer therapies; Cell Proliferation - drug effects; chemoprevention; eupafolin; Flavones - therapeutic use; Herbal medicine; Humans; Kinases; Male; Mice, Inbred BALB C; Mice, Nude; Models, Molecular; Mutation; phosphatidylinositol 3-kinase; Phosphatidylinositol 3-Kinases - metabolism; Prostate - drug effects; Prostate - metabolism; Prostate - pathology; Prostate cancer; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Proto-Oncogene Proteins c-akt - metabolism; Signal Transduction - drug effects; prostate cancer; chemoprevention; Akt; eupafolin; phosphatidylinositol 3-kinase
• ISSN: 0899-1987; 1098-2744
• DOI: 10.1002/mc.22139

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. © 2014 Wiley Periodicals, Inc.