title: 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.
abstract: 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.
authors.affiliation: Center for Core Research Facilities, Daegu Gyeongbuk Institute of Science and Technology, Daegu 711-873, Republic of Korea.
authors.forename: Jin-Woo
authors.initials: JW
authors.lastname: Jeong
authors.affiliation: Department of Horticultural Bioscience, College of Natural Resource and Life Sciences, Busan National University, Miryang 627-706, Republic of Korea.
authors.forename: Sejin
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Molecular Biology, Dongeui University, Busan 614-714, Republic of Korea.
authors.forename: Cheol
authors.initials: C
authors.lastname: Park
authors.affiliation: Research Institute of Biomedical Engineering and Department of Medicine, Catholic University of Daegu School of Medicine, Daegu 705‑718, Republic of Korea.
authors.forename: Young-Chae
authors.initials: YC
authors.lastname: Chang
authors.affiliation: Department of Biology Education, Daegu University, Gyeongbuk 712-714, Republic of Korea.
authors.forename: Dong-Oh
authors.initials: DO
authors.lastname: Moon
authors.affiliation: Team for Scientification of Korean Medical Intervention (BK21 Plus) and Department of Herbal Pharmacology, College of Oriental Medicine, Daegu Haany University, Daegu 706-828, Republic of Korea.
authors.forename: Sung Ok
authors.initials: SO
authors.lastname: Kim
authors.affiliation: Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Jeju 690‑756, Republic of Korea.
authors.forename: Gi-Young
authors.initials: GY
authors.lastname: Kim
authors.affiliation: Departments of Parasitology and Genetics, Kosin University College of Medicine, Seo-gu, Busan 602‑702, Republic of Korea.
authors.forename: Hee-Jae
authors.initials: HJ
authors.lastname: Cha
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Busan National University, Busan 609‑735, Republic of Korea.
authors.forename: Heui-Soo
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Horticultural Bioscience, College of Natural Resource and Life Sciences, Busan National University, Miryang 627-706, Republic of Korea.
authors.forename: Young-Whan
authors.initials: YW
authors.lastname: Choi
authors.affiliation: Department of Urology, Chungbuk National University College of Medicine, Cheongju 361-804, Republic of Korea.
authors.forename: Wun-Jae
authors.initials: WJ
authors.lastname: Kim
authors.affiliation: Department of Anatomy and Cell Biology, Dong-A University College of Medicine and Mitochondria Hub Regulation Center, Busan 602‑714, Republic of Korea.
authors.forename: Young Hyun
authors.initials: YH
authors.lastname: Yoo
authors.affiliation: Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan 614‑052, Republic of Korea.
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001596:Benzylamines / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D005737:Garlic / Q000737:chemistry*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007938:Leukemia / Q000473:pathology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D020298:U937 Cells
chemical_list: D000970:Antineoplastic Agents; D001596:Benzylamines; C029991:N-methylbenzylamine