| Aloe-emodin suppresses prostate cancer by targeting the mTOR complex 2. | |
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MedLine Citation:
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PMID: 22532249 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-04-24 |
Journal Detail:
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Title: Carcinogenesis Volume: 33 ISSN: 1460-2180 ISO Abbreviation: Carcinogenesis Publication Date: 2012 Jul |
Date Detail:
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Created Date: 2012-07-30 Completed Date: 2012-10-16 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 8008055 Medline TA: Carcinogenesis Country: England |
Other Details:
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Languages: eng Pagination: 1406-11 Citation Subset: IM |
Affiliation:
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The World Class Institute and Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology, Ochang, Cheongwon 363-883, Republic of Korea. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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:
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0/Anthraquinones; C8IYT9CR7C/aloe emodin; EC 2.7.1.1/MTOR protein, human; EC 2.7.1.1/TOR Serine-Threonine Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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