Novel anthraquinone derivatives: synthesis via click chemistry approach and their induction of apoptosis in BGC gastric cancer cells via reactive oxygen species (ROS)-dependent mitochondrial pathway.
Three water soluble anthraquinone derivatives were designed and synthesized employing click chemistry to prepare novel and potent antitumor drugs. An MTT assay indicated that all compounds had significant inhibitory activity against BGC gastric cancer cells in vitro. Apoptosis induced by these compounds was observed by flow cytometry and laser confocal microscopy. Mechanistic analysis showed that these compounds induced the generation of several reactive oxygen species, the loss of mitochondrial membrane potential (Delta psi m), the transition of mitochondrial permeability, and the release of cytochrome C from the mitochondrion to cytoplasm. These results suggest that the anthraquinones might be potential lead compounds for the cancer chemotherapy.
Wang
Shaoru
S
College of Chemistry and Molecular Sciences, Wuhan University, Hubei, Wuhan 430072, PR China.
Wang
Qilong
Q
Wang
Yan
Y
Liu
Lin
L
Weng
Xiaocheng
X
Li
Guorui
G
Zhang
Xiaolian
X
Zhou
Xiang
X
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003593:Cytoplasm / Q000378:metabolism; D015195:Drug Design; D005434:Flow Cytometry; D006801:Humans; D020128:Inhibitory Concentration 50; D008564:Membrane Potentials; D018613:Microscopy, Confocal / Q000379:methods; D008928:Mitochondria / Q000378:metabolism*; D010539:Permeability; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue