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Hirsutenone in Alnus extract inhibits akt activity and suppresses prostate cancer cell proliferation
Author(s) -
Kang Soouk,
Kim JongEun,
Li Yan,
Jung Sung Keun,
Song Nu Ry,
Thimmegowda N.R.,
Kim Bo Yeon,
Lee Hyong Joo,
Bode Ann M.,
Dong Zigang,
Lee Ki Won
Publication year - 2015
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.22211
Subject(s) - lncap , protein kinase b , biology , prostate cancer , pi3k/akt/mtor pathway , propidium iodide , cancer research , cancer cell , akt1 , cancer , cell growth , apoptosis , biochemistry , pharmacology , programmed cell death , genetics
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. © 2014 Wiley Periodicals, Inc.