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: Soouk Kang, Jong-Eun Kim, Yan Li, Sung Keun Jung, Nu Ry Song, N R Thimmegowda, Bo Yeon Kim, Hyong Joo Lee, Ann M Bode, Zigang Dong, Ki Won Lee
• Journal: Molecular carcinogenesis (Mol Carcinog) Vol. 54 Issue 11 Pg. 1354-62 (Nov 2015) ISSN: 1098-2744 [Electronic] United States
• PMID: 25213146 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 Wiley Periodicals, Inc.

Chemical References

• Catechols
• Diarylheptanoids
• Plant Extracts
• hirsutenone
• Adenosine Triphosphate
• MTOR protein, human
• Proto-Oncogene Proteins c-akt
• TOR Serine-Threonine Kinases

Topics

• Adenosine Triphosphate (metabolism)
• Alnus (chemistry)
• Apoptosis (drug effects)
• Catechols (pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Diarylheptanoids (pharmacology)
• Humans
• Male
• Phosphorylation (drug effects)
• Plant Extracts (pharmacology)
• Prostatic Neoplasms (drug therapy, metabolism)
• Proto-Oncogene Proteins c-akt (antagonists & inhibitors)
• Signal Transduction (drug effects)
• TOR Serine-Threonine Kinases (metabolism)