Anti-angiogenic and anti-tumor apoptotic activities of a topoisomerase II inhibiting agent SJ-8026.
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| Abstract |
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.
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| Authors | Eui-Yeun Yi, Eun-Joo Jeong, Dong-Wook Kang, Jeong-Ho Joo, Ho-Seok Kwon, Sun-Hwan Lee, Si-Kyung Park, Sun-Gan Chung, Eui-Hwan Cho, Yung-Jin Kim |
| Journal | International journal of oncology (Int J Oncol) Vol. 26 Issue 6 Pg. 1613-20 (Jun 2005) ISSN: 1019-6439 [Print] Greece |
| PMID | 15870877 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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