title: Hirsutenone in Alnus extract inhibits akt activity and suppresses prostate cancer cell proliferation.
abstract: Although specific compounds found in some East Asian traditional medicines have been shown to exhibit bioactive properties, their molecular mechanisms of action remain elusive. The bark of the Alnus species has been used for the treatment of various pathological conditions including hemorrhage, alcoholism, fever, diarrhea, skin diseases, inflammation, and cancer in East Asia for centuries. In this study, we show that hirsutenone, a bioactive compound in Alnus japonica, exhibits anti-cancer effects against prostate cancer through a direct physical inhibition of Akt1/2. Hirsutenone suppressed anchorage-dependent and independent cell growth of PC3 and LNCaP human prostate cancer cells. Annexin V and Propidium iodide (PI) staining results demonstrated that hirsutenone strongly induces apoptotic cell death in both PC3 and LNCaP cells. Furthermore, treatment of hirsutenone attenuated phosphorylation of mammalian target of rapamycin (mTOR), a downstream substrate of Akt, without affecting Akt phosphorylation. Kinase and pull-down assay results clearly show that hirsutenone inhibits Akt1 and 2 by direct binding in an adenosine triphosphate (ATP)-noncompetitive manner in vitro and ex vivo. Our results show that hirsutenone suppresses human prostate cancer by targeting Akt1 and 2 as a key component to explain for anti-cancer activity of Alnus species.
authors.affiliation: WCU Biomodulation Major, Center for Food and Bioconvergence, Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea.|The Hormel Institute, University of Minnesota, Austin, Minnesota.
authors.forename: Soouk
authors.initials: S
authors.lastname: Kang
authors.affiliation: WCU Biomodulation Major, Center for Food and Bioconvergence, Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea.|The Hormel Institute, University of Minnesota, Austin, Minnesota.
authors.forename: Jong-Eun
authors.initials: JE
authors.lastname: Kim
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, Minnesota.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: WCU Biomodulation Major, Center for Food and Bioconvergence, Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea.|Division of Metabolism and Functionality Research, Korea Food Research Institute, Seongnam, Republic of Korea.
authors.forename: Sung Keun
authors.initials: SK
authors.lastname: Jung
authors.affiliation: Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Republic of Korea.
authors.forename: Nu Ry
authors.initials: NR
authors.lastname: Song
authors.affiliation: Chemical Biology Research Center and World Class Institute (WCI), Korea Research Institute of Bioscience and Biotechnology, Ochang, Republic of Korea.
authors.forename: N R
authors.initials: NR
authors.lastname: Thimmegowda
authors.affiliation: Chemical Biology Research Center and World Class Institute (WCI), Korea Research Institute of Bioscience and Biotechnology, Ochang, Republic of Korea.
authors.forename: Bo Yeon
authors.initials: BY
authors.lastname: Kim
authors.affiliation: Research Institute of Bio Food Industry, Institute of Green Bio Science and Technology, Seoul National University, Pyeongchang, Republic of Korea.
authors.forename: Hyong Joo
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, Minnesota.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Bode
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, Minnesota. zgdong@hi.umn.edu.
authors.forename: Zigang
authors.initials: Z
authors.lastname: Dong
authors.affiliation: WCU Biomodulation Major, Center for Food and Bioconvergence, Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea. kiwon@snu.ac.kr.|Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Republic of Korea. kiwon@snu.ac.kr.|Research Institute of Bio Food Industry, Institute of Green Bio Science and Technology, Seoul National University, Pyeongchang, Republic of Korea. kiwon@snu.ac.kr.
authors.forename: Ki Won
authors.initials: KW
authors.lastname: Lee
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D029661:Alnus / Q000737:chemistry*; D017209:Apoptosis / Q000187:drug effects; D002396:Catechols / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D036381:Diarylheptanoids / Q000494:pharmacology*; D006801:Humans; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D002396:Catechols; D036381:Diarylheptanoids; D010936:Plant Extracts; C508777:hirsutenone; D000255:Adenosine Triphosphate; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases
keywords: akt; hirsutenone; proliferation; prostate cancer