Document Detail


Aloe-emodin suppresses prostate cancer by targeting the mTOR complex 2.
MedLine Citation:
PMID:  22532249     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Phosphatidylinositol 3-kinase (PI3-K) amplification and phosphatase and tensin homolog (PTEN) deletion-caused Akt activation contribute to the development of prostate cancer. Mammalian target of rapamycin complex 2 (mTORC2) is a kinase complex comprised of mTOR, Rictor, mSin1, mLST8/GβL and PRR5 and functions in the phosphorylation of Akt at Ser473. Herein, we report that mTORC2 plays an important role in PC3 androgen refractory prostate cell proliferation and anchorage-independent growth. Aloe-emodin, a natural compound found in aloe, inhibited both proliferation and anchorage-independent growth of PC3 cells. Protein content analysis suggested that activation of the downstream substrates of mTORC2, Akt and PKCα, was inhibited by aloe-emodin treatment. Pull-down assay and in vitro kinase assay results indicated that aloe-emodin could bind with mTORC2 in cells and inhibit its kinase activity. Aloe-emodin also exhibited tumor suppression effects in vivo in an athymic nude mouse model. Collectively, our data suggest that mTORC2 plays an important role in prostate cancer development and aloe-emodin suppresses prostate cancer progression by targeting mTORC2.
Authors:
Kangdong Liu; Chanmi Park; Shengqing Li; Ki Won Lee; Haidan Liu; Long He; Nak Kyun Soung; Jong Seog Ahn; Ann M Bode; Ziming Dong; Bo Yeon Kim; Zigang Dong
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-04-24
Journal Detail:
Title:  Carcinogenesis     Volume:  33     ISSN:  1460-2180     ISO Abbreviation:  Carcinogenesis     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-07-30     Completed Date:  2012-10-16     Revised Date:  2013-07-02    
Medline Journal Info:
Nlm Unique ID:  8008055     Medline TA:  Carcinogenesis     Country:  England    
Other Details:
Languages:  eng     Pagination:  1406-11     Citation Subset:  IM    
Affiliation:
The World Class Institute and Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology, Ochang, Cheongwon 363-883, Republic of Korea.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anthraquinones / pharmacology*
Cell Line, Tumor
Humans
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Prostatic Neoplasms / metabolism,  prevention & control*
Signal Transduction
TOR Serine-Threonine Kinases / drug effects*,  metabolism
Grant Support
ID/Acronym/Agency:
CA027502/CA/NCI NIH HHS; CA077646/CA/NCI NIH HHS; CA120388/CA/NCI NIH HHS; ES016548/ES/NIEHS NIH HHS; R37CA081064/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Anthraquinones; C8IYT9CR7C/aloe emodin; EC 2.7.1.1/MTOR protein, human; EC 2.7.1.1/TOR Serine-Threonine Kinases
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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