title: Apoptosis of human prostate cancer cells induced by marine actinomycin X2 through the mTOR pathway compounded by MiRNA144.
abstract: The present study aimed to determine whether actinomycin X2 (AX2) intercepted the mTOR/PTEN/PI3K/Akt signaling pathway to inhibit human prostate cancer cells (PC-3) in vitro. The effects of AX2 on mTOR, PTEN, PI3K, and Akt at the protein level and mRNA were determined by western blotting and real-time reverse transcription-PCR (RT-PCR), respectively. Concurrently, the effects of AX2 on expression levels of MiRNA144 and MiRNA126 in PC-3 were measured by real-time RT-PCR. The association of MiRNA144 with 3'-UTR of mTOR was identified using the Dual-Luciferase Reporter Gene System. The direct effect of MIRNA144 on the mTOR/PTEN/PI3K/Akt pathway was determined by real-time RT-PCR and western blotting. Apoptosis of PC-3 cells induced by AX2 was determined by MTT and flow cytometry. The results indicated that mTOR/PTEN/PI3K/Akt were decreased and PTEN was increased by AX (1, 10 µmol/l) at protein and mRNA levels in a dose-dependent manner. MiRNA144 was decreased, whereas MiRNA126 was increased by AX2. MiRNA144 associated with 3'-UTR of mTOR was corroborated. Overexpression of MiRNA144 decreased mTOR, but did not affect PTEN, PI3K, or Akt. The proliferation rates of AX2 on PC-3 cells were decreased. It suggests that AX2 induces apoptosis of PC-3 cells via meddling in the mTOR/PTEN/PI3K/Akt signaling pathway, but those effects are compounded by MiRNA144. Both AX2 and MiRNA144 intercept the signaling in different ways but cross on mTOR.
authors.affiliation: aDepartment of Urology, Guangzhou General Hospital of Guangzhou Military Command bGuangzhou Huabo Bio-pharmaceutical Research Institute cSchool of Bioscience and Bioengineering, South China University of Technology dDepartment of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Shuilin
authors.initials: S
authors.lastname: Xie
authors.forename: Yukun
authors.initials: Y
authors.lastname: Wu
authors.forename: Meinian
authors.initials: M
authors.lastname: Xu
authors.forename: Chunping
authors.initials: C
authors.lastname: Ao
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Qinsong
authors.initials: Q
authors.lastname: Zeng
authors.forename: Weilie
authors.initials: W
authors.lastname: Hu
authors.forename: Ming
authors.initials: M
authors.lastname: Li
mesh_terms: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D059001:Aquatic Organisms; D045744:Cell Line, Tumor / Q000187:drug effects; D003609:Dactinomycin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents; D003609:Dactinomycin; D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C527111:MIRN126 microRNA, human; C554293:MIRN144 microRNA, human; C000608363:actinomycin X2; C546842:MTOR protein, human