title: Synthesized tetrahydroisoquinoline alkaloid exerts anticancer effects at least in part by suppressing NF-κB-regulated proteins in A549 human lung cancer cells.
abstract: CKD-712, a newly synthesized tetrahydroisoquinoline (THI) and an enantiomer (S form) of YS 49 (a derivative of higenamine) has been reported to suppress nuclear factor-κB (NF-κB) activity in normal cells. In the present study, we investigated the anticancer effects of THI at a low concentration where CKD-712 did not induce cell death in normal cells. At the range of concentrations used, CKD-712 induced cell growth arrest, and inhibited the invasion and motility of A549 cells as determined by cell cycle analysis, a Matrigel-coated chamber assay, and a wound-healing assay, respectively. CKD-712 suppressed MMP-9, but not MMP-2 and other NF-κB-regulated proteins involved in cancer metastasis such as VEGF. Moreover, CKD-712 induced cell cycle arrest at G2M phase by suppressing cyclin A, cyclin B and CDK-1 expression. Taken together, these data suggested that CKD-712 may exert anticancer effects by suppressing NF-κB pathways and inducing cell cycle arrest at G2M phase.
authors.affiliation: Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-702, Republic of Korea.
authors.forename: Won Sup
authors.initials: WS
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-702, Republic of Korea.
authors.forename: Jeong Won
authors.initials: JW
authors.lastname: Yun
authors.affiliation: Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-702, Republic of Korea.
authors.forename: Arulkumar
authors.initials: A
authors.lastname: Nagappan
authors.affiliation: Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-702, Republic of Korea.
authors.forename: Jing Nan
authors.initials: JN
authors.lastname: Lu
authors.affiliation: Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-702, Republic of Korea.
authors.forename: Min Jeong
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: Department of Pathology, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-702, Republic of Korea.
authors.forename: Jeong-Hee
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Emergency Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-702, Republic of Korea.
authors.forename: Dong Hoon
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-702, Republic of Korea.
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
authors.affiliation: Department of Biochemistry, Dongeui University College of Oriental Medicine and Department of Biomaterial Control (BK21 program), Dongeui University Graduate School, Busan 614-052, Republic of Korea.
authors.forename: Hye Jung
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-702, Republic of Korea.
authors.forename: Ki Churl
authors.initials: KC
authors.lastname: Chang
authors.affiliation: Department of Neurosurgery, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-702, Republic of Korea.
authors.forename: Jin-Myung
authors.initials: JM
authors.lastname: Jung
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D016328:NF-kappa B / Q000187:drug effects* / Q000378:metabolism; D044005:Tetrahydroisoquinolines / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D016328:NF-kappa B; D044005:Tetrahydroisoquinolines; C090309:YS 49