JOURNAL ARTICLE

Matrine induces apoptosis in acute myeloid leukemia cells by inhibiting the PI3K/Akt/mTOR signaling pathway

Abstract

Matrine has been demonstrated to exert anticancer effects on acute myeloid leukemia (AML) cell lines. However, the mechanisms of matrine in AML remain largely unknown. The present study investigated the anticancer effects and underlying mechanisms of matrine on human AML cells in vitro. THP-1 cell lines were cultured and treated with different doses of matrine (0.4, 0.8, 1.2, 1.6 and 2.0 g/l). The effects of matrine on the cell proliferation were assessed by the Cell Counting Kit-8 assay. The apoptotic effects were evaluated by DAPI and annexin V/propidium iodide staining assays. The effects of the drug on phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/ mechanistic target of rapamycin kinase (mTOR) protein expression were studied by western blot analysis. The results of the present study demonstrated that matrine suppressed the viability of THP-1 cells. The anticancer effects were identified to be dose-dependent and the IC50 value was 1.2 g/l in THP-1 cells. Matrine inhibited cell viability and induced cell apoptosis of AML cell lines in a dose- and time-dependent manner. In addition, it was observed that matrine decreased the expression of phosphorylated (p)-PI3K, p-Akt and p-mTOR in a concentration-dependent manner. However, the expression levels of PI3K, Akt and mTOR remained almost unaltered. These findings indicated that matrine may inhibit cell proliferation and induce apoptosis of AML cells and may be a novel effective chemotherapeutic agent against AML.

Keywords:
Matrine PI3K/AKT/mTOR pathway Protein kinase B Viability assay Propidium iodide Apoptosis Myeloid leukemia Cell growth Chemistry Cancer research Molecular biology Biology Programmed cell death Biochemistry

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1.03
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31
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0.73
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Citation History

Topics

Retinoids in leukemia and cellular processes
Life Sciences →  Biochemistry, Genetics and Molecular Biology →  Molecular Biology
Acute Myeloid Leukemia Research
Health Sciences →  Medicine →  Hematology
Cell death mechanisms and regulation
Life Sciences →  Biochemistry, Genetics and Molecular Biology →  Molecular Biology

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JOURNAL ARTICLE

Targeting PI3K/AKT/mTOR signaling in Acute Myeloid Leukemia

Huu NguyenThi DoQuoc Trung LyHoang Anh PhamDang NguyenLe Truong NguyenLiem PhanXuan T. LeXuan LeNguyenB SteffenC Muller-TidowJ SchwableW BerdelH ServeM SmithM BarnettR BassanG GattaC TondiniW KernJ WuW WongF KhosraviM MindenL PennP SujobertV BardetP Cornillet-LefebvreJ HayflickN PrieF VerdierB VanhaesebroeckO MullerF PesceN IfrahM Hunault-BergerC BerthouB VillemagneE JourdanB AudhuyE SolaryB WitzJ HarousseauC HimberlinT LamyB LioureJ CahnF DreyfusP MayeuxC LacombeD BouscaryJ TamburiniC ElieV BardetN ChapuisS ParkP BroetP Cornillet-LefebvreB LioureV UgoO BlanchetN IfrahF WitzF DreyfusP MayeuxC LacombeD BouscaryL SteelmanS AbramsJ WhelanF BertrandD LudwigJ BaseckeM LibraF StivalaM MilellaA TafuriP LunghiA BonatiA MartelliJ MccubreyK PetropoulosN ArseniC SchesslC StadlerV RawatA DeshpandeB HeilmeierW HiddemannL Quintanilla-MartinezS BohlanderM Feuring-BuskeC BuskeM GuzmanS NeeringD UpchurchB GrimesD HowardD RizzieriS LugerC JordanC BrandtsB SarginM RodeC BiermannB LindtnerJ SchwableH BuergerC Muller-TidowC ChoudharyM McmahonW BerdelH ServeY MinJ EomJ CheongH MaengJ KimH JeungS LeeM LeeJ HahnY KoA MartelliP TazzariC EvangelistiF ChiariniW BlalockA BilliL ManzoliJ MccubreyL CoccoR PolakM BuitenhuisB MarkmanR DienstmannJ TaberneroD FrumanR MeyersL CantleyB HennessyD SmithP RamY LuG MillsK CourtneyR CorcoranJ EngelmanS GruppJ HarmonyL SteelmanS PohnertJ SheltonR FranklinF BertrandJ MccubreyA BrunetS DattaM GreenbergA BellacosaJ TestaS StaalP TsichlisS StaalM HanadaJ FengB HemmingsK NicholsonN AndersonD SabatiniH Erdjument-BromageM LuiP TempstS SnyderE JacintoM HallD GuertinD SabatiniK InokiY LiT ZhuJ WuK GuanX LongY LinS Ortiz-VegaK YonezawaJ AvruchB ManningA TeeM LogsdonJ BlenisL CantleyC GranvilleR MemmottJ GillsP DennisM HolzB BallifS GygiJ BlenisN HayM CampbellW AllenC SawyerB VanhaesebroeckE TrimbleM CampbellE TrimbleB SolomonR PearsonD AltomareJ TestaR ShawL CantleyS UddinA HussainA SirajP ManogaranN Al-JomahA MoorjiV AtizadoF Al-DayelA BelgaumiH El-SolhA EzzatP BaviK Al-KurayaS HornU BergholzM JuckerJ MccubreyL TrumperC StockingJ BaseckeR BortulP TazzariA BilliG TabelliniI MantovaniA CappelliniT GrafoneG MartinelliR ConteA MartelliV PapaP TazzariF ChiariniA CappelliniF RicciA BilliC EvangelistiE OttavianiG MartinelliN TestoniJ MccubreyA MartelliR XuH PelicanoH ZhangF GilesM KeatingP HuangX Nguyen LeS ChanT NgoA RavalK KimR MajetiB MitchellT YapM GarrettM WaltonF RaynaudJ De BonoP WorkmanJ LuoB ManningL CantleyA MartelliM NyakernG TabelliniR BortulP TazzariC EvangelistiL CoccoL NguyenA SesayB MitchellQ XuJ ThompsonM CarrollM HahnW LiC YuM RahmaniP DentS GrantC RecherO Beyne-RauzyC DemurG ChicanneC SantosV MasD BenzaquenG LaurentF HuguetB PayrastreF GilesM AlbitarJ ChengC LindsleyG ChengH YangS NicosiaJ GillsP DennisS ParkN ChapuisJ TamburiniV BardetP Cornillet-LefebvreL WillemsA GreenP MayeuxC LacombeD BouscaryX Nguyen LeB Mitchell

Journal:   Vietnam Journal of Science Year: 2014
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