Salvicine, a novel topoisomerase II inhibitor, exerts its potent anticancer activity by ROS generation.
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.
Meng
Ling-hua
LH
Division of Antitumor Pharmacology, State Key laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Ding
Jian
J
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D004249:DNA Damage / Q000187:drug effects; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D006801:Humans; D009285:Naphthoquinones / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D059005:Topoisomerase II Inhibitors
D000972:Antineoplastic Agents, Phytogenic; D009285:Naphthoquinones; D017382:Reactive Oxygen Species; D059005:Topoisomerase II Inhibitors; C122096:salvicine; D004250:DNA Topoisomerases, Type II