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N-benzyl-N-methyldecan-1-amine, a phenylamine derivative isolated from garlic cloves, induces G2/M phase arrest and apoptosis in U937 human leukemia cells

N-benzyl-N-methyldecan-1-amine, a phenylamine derivative isolated from garlic cloves, induces G2/M phase arrest and apoptosis in U937 human leukemia cells
Jeong, JW[Jeong, Jin-Woo]Park, S[Park, Sejin]Park, C[Park, Cheol]Chang, YC[Chang, Young-Chae]Moon, DO[Moon, Dong-Oh]Kim, SO[Kim, Sung Ok]Kim, GY[Kim, Gi-Young]Cha, HJ[Cha, Hee-Jae]Kim, HS[Kim, Heui-Soo]Choi, YW[Choi, Young-Whan]Kim, WJ[Kim, Wun-Jae]Yoo, YH[Yoo, Young Hyun]Choi, YH[Choi, Yung Hyun]
DGIST Authors
Jeong, JW[Jeong, Jin-Woo]
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Article Type
Aniline DerivativeAntineoplastic ActivityAntineoplastic AgentAntineoplastic AgentsApoptosisBenzylamine DerivativeBenzylaminesCaspase 3Caspase 8Caspase 9Cell ProliferationChemistryConcentration ResponseControlled StudyCyclin Dependent Kinase 1Cyclin Dependent Kinase 2Cyclin Dependent Kinase Inhibitor 1Cytochrome CDrug EffectsDrug MechanismDrug StructureEnzyme ActivationG2 Phase Cell Cycle CheckpointG2 Phase Cell Cycle CheckpointsG2/M ArrestGarlicGene Expression RegulationGene Expression Regulation, NeoplasticGene RepressionHumanHuman CellHumansInhibitor of Apoptosis Protein 1LeukemiaLeukemia U937 CellsMembrane Potential, MitochondrialMitochondrial Membrane PotentialMitosis InhibitionN-Benzyl-N-Methyldecan-1-AmineN-MethylbenzylamineN Benzyl N Methyldecan 1 AmineNicotinamide Adenine Dinucleotide Adenosine Diphosphate RibosyltransferasePathologyPriority JournalProtein BADProtein BaxProtein BCL 2Protein BCL XLProtein BidProtein P53Protein SecretionSignal TransductionU-937 Cell LineU-937 CellsUnclassified DrugWestern BlottingX Linked Inhibitor of Apoptosis
Epidemiological studies indicate that components of garlic (Allium sativum) have anti-proliferative effects against various types of cancer. In the present study, we investigated the effect of newly isolated phenylamine derivative N-benzyl-N-methyldecan-1-amine (NBNMA) from garlic cloves on the inhibition of the growth and apoptosis of human leukemia U937 cells and its potential anticancer mechanism. NBNMA exhibited an antiproliferative effect in U937 cells by inducing cell cycle arrest at the G2/M phase and apoptotic cell death. Western blot analyses revealed that NBNMA decreased the expression of the regulator genes of G2/M phase progression, cyclin dependent kinase (Cdk) 2 and Cdc2 and elevated the expression of the Cdk inhibitor p21WAF1/CIP1 in a p53-independent manner. In addition, NBNMA activated caspase-8 and caspase-9, initiator caspases of the extrinsic and intrinsic pathways of apoptosis, respectively, which led to activation of executioner caspase-3 along with degradation of poly(ADP-ribose) polymerase. NBNMA-induced apoptosis was observed in parallel with an increased ratio of pro-apoptotic Bax and Bad/anti-apoptotic Bcl-2 and Bcl-xL, and inhibition of inhibitor of apoptosis protein (IAP) family members XIAP and cIAP-1. Furthermore, NBNMA-treated cells displayed enhanced release of cytochrome c from the mitochondria into the cytosol concomitant with a loss of mitochondrial membrane potential and downregulation of Bid, suggesting that NBNMA-induced apoptosis occurred via the extrinsic and intrinsic apoptotic pathways with a possible link to Bid protein activity between the two pathways. These results indicate that NBNMA has promising potential to become a novel anticancer agent for the treatment of leukemia. We provide new insight into the mechanisms underlying the anticancer effect of NBNMA.
Spandidos Publications
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