Tanshinone IIA interacts with DNA by minor groove-binding.
Tanshen has long been widely used as a traditional Chinese medicine. Tanshinone IIA (Tan IIA) is the most abundant lipophilic constituent of Tanshen which has antitumor activity but the mechanism is poorly understood. Some preliminary reports hypothesized that it is a DNA intercalator and that the furano-o-quinone moiety could produce free radicals responsible for its cytotoxicity. Here the interaction of Tan IIA with DNA was explored in detail using fluorescence, viscosimetry, and molecular modeling. Tan IIA was found to bind with DNA in the minor groove rather than act as an intercalator. Furthermore, the results of immunofluorescence showed that Tan IIA does not produce free radicals in vivo to damage DNA. The former hypothesis was thus negated. The furan oxygen plays the key role in the antitumor ability of Tan IIA because it is involved in the groove-binding, but not in the production of free radicals. The molecular basis illustrated here could be responsible for all the findings in the structure-relationship studies of tanshinone cytotoxicity.
Zhang
Zhichao
Z
State Key Lab. of Fine Chemicals, Dalian University of Technology, People's Republic of China. zczhang@dlut.edu.cn
Zhang
Jing
J
Jin
Liji
L
Song
Ting
T
Wu
Guiye
G
Gao
Jin
J
D045784:Abietanes; D000465:Algorithms; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D002460:Cell Line; D004247:DNA / Q000737:chemistry* / Q000187:drug effects*; D005455:Fluorescent Antibody Technique; D005663:Furans / Q000737:chemistry; D006801:Humans; D007364:Intercalating Agents / Q000494:pharmacology; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D010616:Phenanthrenes / Q000737:chemistry / Q000494:pharmacology*; D013050:Spectrometry, Fluorescence; D014783:Viscosity
D045784:Abietanes; D000972:Antineoplastic Agents, Phytogenic; D005663:Furans; D007364:Intercalating Agents; D010616:Phenanthrenes; C021751:tanshinone; D004247:DNA