title: Aloe-emodin suppresses prostate cancer by targeting the mTOR complex 2.
abstract: 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.affiliation: The World Class Institute and Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology, Ochang, Cheongwon 363-883, Republic of Korea.
authors.forename: Kangdong
authors.initials: K
authors.lastname: Liu
authors.forename: Chanmi
authors.initials: C
authors.lastname: Park
authors.forename: Shengqing
authors.initials: S
authors.lastname: Li
authors.forename: Ki Won
authors.initials: KW
authors.lastname: Lee
authors.forename: Haidan
authors.initials: H
authors.lastname: Liu
authors.forename: Long
authors.initials: L
authors.lastname: He
authors.forename: Nak Kyun
authors.initials: NK
authors.lastname: Soung
authors.forename: Jong Seog
authors.initials: JS
authors.lastname: Ahn
authors.forename: Ann M
authors.initials: AM
authors.lastname: Bode
authors.forename: Ziming
authors.initials: Z
authors.lastname: Dong
authors.forename: Bo Yeon
authors.initials: BY
authors.lastname: Kim
authors.forename: Zigang
authors.initials: Z
authors.lastname: Dong
mesh_terms: D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000517:prevention & control*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000880:Anthraquinones; C518327:aloe emodin; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases