Abstract
Salvicine is a novel diterpenoid quinone compound obtained by structural modification of a natural product lead isolated from a Chinese herb with potent growth inhibitory activity against a wide spectrum of human tumor cells in vitro and in mice bearing human tumor xenografts. Salvicine has also been found to have a profound cytotoxic effect on multidrug-resisitant (MDR) cells. Moreover, Salvicine significantly reduced the lung metastatic foci of MDA-MB-435 orthotopic xenograft. Recent studies demonstrated that salvicine is a novel non-intercalative topoisomerase II (Topo II) poison by binding to the ATPase domain, promoting DNA-Topo II binding and inhibiting Topo II-mediated DNA relegation and ATP hydrolysis. Further studies have indicated that salcivine-elicited ROS plays a central role in salvicine-induced cellular response including Topo II inhibition, DNA damage, circumventing MDR and tumor cell adhesion inhibition.
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The work was supported in part by grants from the National Natural Science Foundation of China (No 29222003, 39830444, 30070877, 39670840, 39970855, 30271513, 3022803, 30200324, 30330670), the Science Foundation of the Chinese Academy of Sciences (KY-951-A1-301-01-02, KSCX2-SW-202) and Ministry of Science and Technology of China (No 2002AA2Z3461)
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Meng, Lh., Ding, J. Salvicine, a novel topoisomerase II inhibitor, exerts its potent anticancer activity by ROS generation. Acta Pharmacol Sin 28, 1460–1465 (2007). https://doi.org/10.1111/j.1745-7254.2007.00698.x
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DOI: https://doi.org/10.1111/j.1745-7254.2007.00698.x
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