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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]
- Issue Date
- Oncology Reports, 32(1), 373-381
- Article Type
- Aniline Derivative; Antineoplastic Activity; Antineoplastic Agent; Antineoplastic Agents; Apoptosis; Benzylamine Derivative; Benzylamines; Caspase 3; Caspase 8; Caspase 9; Cell Proliferation; Chemistry; Concentration Response; Controlled Study; Cyclin Dependent Kinase 1; Cyclin Dependent Kinase 2; Cyclin Dependent Kinase Inhibitor 1; Cytochrome C; Drug Effects; Drug Mechanism; Drug Structure; Enzyme Activation; G2 Phase Cell Cycle Checkpoint; G2 Phase Cell Cycle Checkpoints; G2/M Arrest; Garlic; Gene Expression Regulation; Gene Expression Regulation, Neoplastic; Gene Repression; Human; Human Cell; Humans; Inhibitor of Apoptosis Protein 1; Leukemia; Leukemia U937 Cells; Membrane Potential, Mitochondrial; Mitochondrial Membrane Potential; Mitosis Inhibition; N-Benzyl-N-Methyldecan-1-Amine; N-Methylbenzylamine; N Benzyl N Methyldecan 1 Amine; Nicotinamide Adenine Dinucleotide Adenosine Diphosphate Ribosyltransferase; Pathology; Priority Journal; Protein BAD; Protein Bax; Protein BCL 2; Protein BCL XL; Protein Bid; Protein P53; Protein Secretion; Signal Transduction; U-937 Cell Line; U-937 Cells; Unclassified Drug; Western Blotting; X 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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