PMID- 25213146
OWN - NLM
STAT- MEDLINE
DCOM- 20160201
LR  - 20211203
IS  - 1098-2744 (Electronic)
IS  - 0899-1987 (Linking)
VI  - 54
IP  - 11
DP  - 2015 Nov
TI  - Hirsutenone in Alnus extract inhibits akt activity and suppresses prostate cancer 
      cell proliferation.
PG  - 1354-62
LID - 10.1002/mc.22211 [doi]
AB  - 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.
CI  - (c) 2014 Wiley Periodicals, Inc.
FAU - Kang, Soouk
AU  - Kang S
AD  - WCU Biomodulation Major, Center for Food and Bioconvergence, Department of 
      Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea.
AD  - The Hormel Institute, University of Minnesota, Austin, Minnesota.
FAU - Kim, Jong-Eun
AU  - Kim JE
AD  - WCU Biomodulation Major, Center for Food and Bioconvergence, Department of 
      Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea.
AD  - The Hormel Institute, University of Minnesota, Austin, Minnesota.
FAU - Li, Yan
AU  - Li Y
AD  - The Hormel Institute, University of Minnesota, Austin, Minnesota.
FAU - Jung, Sung Keun
AU  - Jung SK
AD  - WCU Biomodulation Major, Center for Food and Bioconvergence, Department of 
      Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea.
AD  - Division of Metabolism and Functionality Research, Korea Food Research Institute, 
      Seongnam, Republic of Korea.
FAU - Song, Nu Ry
AU  - Song NR
AD  - Advanced Institutes of Convergence Technology, Seoul National University, Suwon, 
      Republic of Korea.
FAU - Thimmegowda, N R
AU  - Thimmegowda NR
AD  - Chemical Biology Research Center and World Class Institute (WCI), Korea Research 
      Institute of Bioscience and Biotechnology, Ochang, Republic of Korea.
FAU - Kim, Bo Yeon
AU  - Kim BY
AD  - Chemical Biology Research Center and World Class Institute (WCI), Korea Research 
      Institute of Bioscience and Biotechnology, Ochang, Republic of Korea.
FAU - Lee, Hyong Joo
AU  - Lee HJ
AD  - Research Institute of Bio Food Industry, Institute of Green Bio Science and 
      Technology, Seoul National University, Pyeongchang, Republic of Korea.
FAU - Bode, Ann M
AU  - Bode AM
AD  - The Hormel Institute, University of Minnesota, Austin, Minnesota.
FAU - Dong, Zigang
AU  - Dong Z
AD  - The Hormel Institute, University of Minnesota, Austin, Minnesota. 
      zgdong@hi.umn.edu.
FAU - Lee, Ki Won
AU  - Lee KW
AD  - WCU Biomodulation Major, Center for Food and Bioconvergence, Department of 
      Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea. 
      kiwon@snu.ac.kr.
AD  - Advanced Institutes of Convergence Technology, Seoul National University, Suwon, 
      Republic of Korea. kiwon@snu.ac.kr.
AD  - Research Institute of Bio Food Industry, Institute of Green Bio Science and 
      Technology, Seoul National University, Pyeongchang, Republic of Korea. 
      kiwon@snu.ac.kr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140911
PL  - United States
TA  - Mol Carcinog
JT  - Molecular carcinogenesis
JID - 8811105
RN  - 0 (Catechols)
RN  - 0 (Diarylheptanoids)
RN  - 0 (Plant Extracts)
RN  - 0 (hirsutenone)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Adenosine Triphosphate/metabolism
MH  - Alnus/*chemistry
MH  - Apoptosis/drug effects
MH  - Catechols/*pharmacology
MH  - Cell Line, Tumor
MH  - Cell Proliferation/*drug effects
MH  - Diarylheptanoids/*pharmacology
MH  - Humans
MH  - Male
MH  - Phosphorylation/drug effects
MH  - Plant Extracts/*pharmacology
MH  - Prostatic Neoplasms/*drug therapy/*metabolism
MH  - Proto-Oncogene Proteins c-akt/*antagonists & inhibitors
MH  - Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/metabolism
OTO - NOTNLM
OT  - akt
OT  - hirsutenone
OT  - proliferation
OT  - prostate cancer
EDAT- 2014/09/13 06:00
MHDA- 2016/02/02 06:00
CRDT- 2014/09/13 06:00
PHST- 2014/03/27 00:00 [received]
PHST- 2014/06/26 00:00 [revised]
PHST- 2014/07/09 00:00 [accepted]
PHST- 2014/09/13 06:00 [entrez]
PHST- 2014/09/13 06:00 [pubmed]
PHST- 2016/02/02 06:00 [medline]
AID - 10.1002/mc.22211 [doi]
PST - ppublish
SO  - Mol Carcinog. 2015 Nov;54(11):1354-62. doi: 10.1002/mc.22211. Epub 2014 Sep 11.