title: Torin2 Potentiates Anticancer Effects on Adult T-Cell Leukemia/Lymphoma by Inhibiting Mammalian Target of Rapamycin.
abstract: BACKGROUND
  Torin2 is a second-generation ATP-competitive inhibitor of the mammalian target of rapamycin (mTOR). Dysregulation of mTOR signaling pathway, consisting of mTOR complexes mTORC1 and mTORC2, is a promising therapeutic target in some human malignancies. We examined antitumor effects of Torin2 in adult T-cell leukemia/lymphoma (ATL)-related cell lines compared to those of rapamycin, a classical mTOR inhibitor.
  
  
  METHODS
  Cell growth was monitored by detecting viable cells with Cell Counting Kit-8 or trypan blue. Cell cycle was studied by flow cytometric analysis. The phosphorylation status of proteins in the mTOR signaling pathway was examined by western blot analysis.
  
  
  RESULTS
  Torin2 exhibited greater efficacy in cell growth inhibition than rapamycin, associated with a strong reduction of phosphorylated v-akt murine thymoma viral oncogene homolog (AKT) (Ser 473), that is downstream of mTORC2.
  
  
  CONCLUSIONS
  Since mTORC2 activates AKT, Torin2 might inhibit both mTORC1 and mTORC2, resulting in stronger growth inhibition of ATL cells.
authors.affiliation: Department of Laboratory Medicine, Saga University Hospital, Nabeshima, Saga, Japan.
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Division of Hematology, Respiratory Medicine and Oncology, Faculty of Medicine, Saga University, Nabeshima, Saga, Japan.
authors.forename: Akemi
authors.initials: A
authors.lastname: Sato
authors.affiliation: Division of Hematology, Respiratory Medicine and Oncology, Faculty of Medicine, Saga University, Nabeshima, Saga, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Kobayashi-Watanabe
authors.affiliation: Division of Hematology, Respiratory Medicine and Oncology, Faculty of Medicine, Saga University, Nabeshima, Saga, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Sueoka-Aragane
authors.affiliation: Division of Hematology, Respiratory Medicine and Oncology, Faculty of Medicine, Saga University, Nabeshima, Saga, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Kimura
authors.affiliation: Department of Laboratory Medicine, Saga University Hospital, Nabeshima, Saga, Japan Department of Clinical Laboratory Medicine, Faculty of Medicine, Saga University, Nabeshima, Saga, Japan sueokae@cc.saga-u.ac.jp.
authors.forename: Eisaburo
authors.initials: E
authors.lastname: Sueoka
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005047:Etoposide / Q000494:pharmacology; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D046912:Multiprotein Complexes / Q000037:antagonists & inhibitors / Q000378:metabolism; D009287:Naphthyridines / Q000494:pharmacology*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: C558529:9-(6-aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo(h)(1,6)naphthyridin-2(1H)-one; D000970:Antineoplastic Agents; D046912:Multiprotein Complexes; D009287:Naphthyridines; D047428:Protein Kinase Inhibitors; D005047:Etoposide; C546842:MTOR protein, human; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
keywords: AKT; Adult T-cell leukemia/lymphoma; growth inhibition; mammalian target of rapamycin