title: Anti-angiogenic and anti-tumor apoptotic activities of SJ-8002, a new piperazine derivative.
abstract: A new piperazine derivative, SJ-8002, is a synthetic anti-cancer agent which exhibits microtubule-inhibiting activities. In this study, we investigated the possibility that this compound inhibits angiogenesis and induces tumor-cell apoptosis using bovine aortic endothelial cells (BAECs) and human hepatocellular carcinoma cells (HepG2) as a model system, respectively. In vivo, SJ-8002 decreased the neovascularization of chick embryos and the basic fibroblast growth factor (bFGF)-induced angiogenesis in the chorioallantoic membrane (CAM) and the mouse Matrigel implants, respectively. In vitro, SJ-8002 treatment resulted in the inhibition of proliferation, migration, invasion and tube formation, and of matrix metalloproteinase-2 (MMP-2) expression in BAECs. In addition, the SJ-8002 treatment in HepG2 cells reduced cell viability, and caused the production of fragmented DNA and the morphological changes corresponding to apoptosis including condensed and fragmented DNA in a concentration-dependent manner. SJ-8002 also elicited the release of cytochrome c and the activation of caspase-3. Therefore, it is possible that SJ-8002 functions as both angiogenesis inhibitor and apoptosis inducer. Taken together, these results suggest that SJ-8002 may be a candidate for strong anti-cancer agent with the ability to inhibit the angiogenesis of endothelial cells and to induce the apoptosis of tumor cells.
authors.affiliation: Department of Molecular Biology, Pusan National University, Pusan 609-735, Korea.
authors.forename: Eui-Yeun
authors.initials: EY
authors.lastname: Yi
authors.forename: Eun-Joo
authors.initials: EJ
authors.lastname: Jeong
authors.forename: Hyun Seok
authors.initials: HS
authors.lastname: Song
authors.forename: Mi-Sook
authors.initials: MS
authors.lastname: Lee
authors.forename: Dong-Wook
authors.initials: DW
authors.lastname: Kang
authors.forename: Jeong-Ho
authors.initials: JH
authors.lastname: Joo
authors.forename: Ho-Seok
authors.initials: HS
authors.lastname: Kwon
authors.forename: Sun-Hwan
authors.initials: SH
authors.lastname: Lee
authors.forename: Si-Kyung
authors.initials: SK
authors.lastname: Park
authors.forename: Sun-Gan
authors.initials: SG
authors.lastname: Chung
authors.forename: Eui-Hwan
authors.initials: EH
authors.lastname: Cho
authors.forename: Yung-Jin
authors.initials: YJ
authors.lastname: Kim
mesh_terms: D000631:Aminopyridines / Q000737:chemistry / Q000494:pharmacology*; D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis; D001681:Biological Assay; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002642:Chick Embryo; D003094:Collagen / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004338:Drug Combinations; D007797:Laminin / Q000187:drug effects; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D000077489:Piperazine; D010879:Piperazines / Q000737:chemistry / Q000494:pharmacology*; D011509:Proteoglycans / Q000187:drug effects
chemical_list: C495454:4-(3,5-dimethylphenyl)piperazine-1-carboxylic acid (2-methoxy-5,6-dimethylpyridin-3-yl)amide; D000631:Aminopyridines; D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D004338:Drug Combinations; D007797:Laminin; D010879:Piperazines; D011509:Proteoglycans; C059485:matrigel; D000077489:Piperazine; D003094:Collagen; D045304:Cytochromes c; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D020778:Matrix Metalloproteinase 2