Anti-angiogenic and anti-tumor apoptotic activities of a topoisomerase II inhibiting agent SJ-8026.
A new piperazine derivative, SJ-8026, is a synthetic anti-cancer agent which exhibits topoisomerase II-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. in vivo, SJ-8026 decreased the neovascularization of chick embryos and the basic fibroblast growth factor-induced angiogenesis in the chorioallantoic membrane and the mouse Matrigel implants. in vitro, SJ-8026 treatment resulted in the inhibition of proliferation, migration, invasion and tube formation in BAECs. In addition, the treatment of SJ-8026 in HepG2 cells reduced the cell viability, and caused the production of fragmented DNA and the morphological changes corresponding to apoptosis including condensed and fragmented DNA. SJ-8026 also elicited the release of cytochrome c and the activation of caspase-3. Therefore, it is possible that SJ-8026 functions as both angiogenesis inhibitor and apoptosis inducer. Taken together, these results suggest that SJ-8026 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, Busan 609-735, Korea.
Jeong
Eun-Joo
EJ
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
D000166:Acridines / Q000494:pharmacology*; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D059005:Topoisomerase II Inhibitors
D000166:Acridines; D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; C502298:SJ-8026; D059005:Topoisomerase II Inhibitors; D045304:Cytochromes c; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases