Eupafolin suppresses prostate cancer by targeting phosphatidylinositol 3-kinase-mediated Akt signaling.
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.
World Class Institute, Korea Research Institute of Bioscience and Biotechnology, Ochang, Republic of Korea.|The Hormel Institute, University of Minnesota, Austin, Minnesota.|The Affiliated Cancer Hospital, Zhengzhou University, Zhengzhou, China.|Basic Medical College, Zhengzhou University, Zhengzhou, China.
Kangdong
K
Liu
World Class Institute, Korea Research Institute of Bioscience and Biotechnology, Ochang, Republic of Korea.|Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology, Ochang, Republic of Korea.
Chanmi
C
Park
The Hormel Institute, University of Minnesota, Austin, Minnesota.
Hanyong
H
Chen
World Class Institute, Korea Research Institute of Bioscience and Biotechnology, Ochang, Republic of Korea.
Joonsung
J
Hwang
World Class Institute, Korea Research Institute of Bioscience and Biotechnology, Ochang, Republic of Korea.
N R
NR
Thimmegowda
Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology, Ochang, Republic of Korea.
Eun Young
EY
Bae
World Class Institute, Korea Research Institute of Bioscience and Biotechnology, Ochang, Republic of Korea.
Ki Won
KW
Lee
The Hormel Institute, University of Minnesota, Austin, Minnesota.
Hong-Gyum
HG
Kim
World Class Institute, Korea Research Institute of Bioscience and Biotechnology, Ochang, Republic of Korea.|Department of Cardiothoracic Surgery, Clinical Center for Gene Diagnosis and Therapy, The Second Xiangya Hospital, Central South University, Changsha, China.
Haidan
H
Liu
World Class Institute, Korea Research Institute of Bioscience and Biotechnology, Ochang, Republic of Korea.
Nak Kyun
NK
Soung
The Hormel Institute, University of Minnesota, Austin, Minnesota.
Cong
C
Peng
Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology, Ochang, Republic of Korea.
Jae Hyuk
JH
Jang
Department of Biochemistry, College of Natural Sciences, Chung Nam National University, Yuseonggu, Republic of Korea.
Kyoon Eon
KE
Kim
Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology, Ochang, Republic of Korea.
Jong Seog
JS
Ahn
The Hormel Institute, University of Minnesota, Austin, Minnesota.
Ann M
AM
Bode
Basic Medical College, Zhengzhou University, Zhengzhou, China.
Ziming
Z
Dong
World Class Institute, Korea Research Institute of Bioscience and Biotechnology, Ochang, Republic of Korea.|Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology, Ochang, Republic of Korea.
Bo Yeon
BY
Kim
World Class Institute, Korea Research Institute of Bioscience and Biotechnology, Ochang, Republic of Korea.|The Hormel Institute, University of Minnesota, Austin, Minnesota.|Basic Medical College, Zhengzhou University, Zhengzhou, China.
Zigang
Z
Dong
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects; D047309:Flavones / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008958:Models, Molecular; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011467:Prostate / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
D000972:Antineoplastic Agents, Phytogenic; D047309:Flavones; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C503624:eupafolin
Akt; chemoprevention; eupafolin; phosphatidylinositol 3-kinase; prostate cancer