title: Alisertib induces apoptosis and autophagy through targeting the AKT/mTOR/AMPK/p38 pathway in leukemic cells.
abstract: Alisertib, a potent and selective Aurora kinase A inhibitor, has been demonstrated to exert potent anti-cancer effects in pre-clinical and clinical studies. However, mechanisms of action of alisertib, including the molecular pathways involved in alisertib-induced apoptosis and autophagy of leukemic cells, have remained elusive. The aim of the present study was to investigate the effects of alisertib on cell growth, apoptosis and autophagy and to delineate the possible molecular mechanisms in leukemic cells. Acid phosphatase, MTT and Annexin V/propidium iodide staining assays as well as immunostaining for light chain 3B showed that treatment of the REH leukemia cell line with alisertib exerted potent growth inhibitory effects, and induced apoptosis and autophagy in a dose‑dependent manner. Western blot analysis indicated that these effects may be attributed to the suppression of the activity of the Akt/mammalian target of rapamycin/5'-AMP-dependent kinase/p38 mitogen-activated protein kinase signaling pathways in REH cells. The present study confirmed that alisertib may represent a promising autophagy-inducing drug for the treatment of leukemia and shed light on its molecular mechanism of action.
authors.affiliation: The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Fu
authors.affiliation: The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Meng
authors.initials: M
authors.lastname: Gao
authors.affiliation: The First Department of Respiratory Medicine, Central Hospital of Zhuzhou, Zhuzhou, Hunan 412000, P.R. China.
authors.forename: Lingli
authors.initials: L
authors.lastname: Quan
authors.affiliation: The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Rong
authors.initials: R
authors.lastname: Gui
authors.affiliation: The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D001381:Azepines / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D007938:Leukemia; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D001381:Azepines; C550258:MLN 8237; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases