Open AccessSalvicine, a novel topoisomerase II inhibitor, exerts its potent anticancer activity by ROS generation 1
Author(s) -
MENG Linghua,
DING Jian
Publication year - 2007
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2007.00698.x
Subject(s) - topoisomerase , in vitro , natural product , chemistry , multiple drug resistance , cytotoxic t cell , pharmacology , topoisomerase inhibitor , cytotoxicity , cancer research , biology , biochemistry , antibiotics
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.