Anti-angiogenic and anti-tumor apoptotic activities of SJ-8002, a new piperazine derivative.
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.
Yi
Eui-Yeun
EY
Department of Molecular Biology, Pusan National University, Pusan 609-735, Korea.
Jeong
Eun-Joo
EJ
Song
Hyun Seok
HS
Lee
Mi-Sook
MS
Kang
Dong-Wook
DW
Joo
Jeong-Ho
JH
Kwon
Ho-Seok
HS
Lee
Sun-Hwan
SH
Park
Si-Kyung
SK
Chung
Sun-Gan
SG
Cho
Eui-Hwan
EH
Kim
Yung-Jin
YJ
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
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