Caspase-3-dependent apoptosis of citreamicin ε-induced heLa iells Is associated with reactive oxygen species generation
KAUST DepartmentPhysical Sciences and Engineering (PSE) Division
Imaging and Characterization Core Lab
Advanced Nanofabrication, Imaging and Characterization Core Lab
Materials Science and Engineering Program
Permanent link to this recordhttp://hdl.handle.net/10754/562863
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AbstractCitreamicins, members of the polycyclic xanthone family, are promising antitumor agents that are produced by Streptomyces species. Two diastereomers, citreamicin ε A (1) and B (2), were isolated from a marine-derived Streptomyces species. The relative configurations of these two diastereomers were determined using NMR spectroscopy and successful crystallization of citreamicin ε A (1). Both diastereomers showed potent cytotoxic activity against HeLa (cervical cancer) and HepG2 (hepatic carcinoma) cells with IC 50 values ranging from 30 to 100 nM. The terminal deoxynucleotidyl transferase dUTP nick-end labeling assay confirmed that citreamicin ε A (1) induced cellular apoptosis, and Western blot analysis showed that apoptosis occurred via activation of caspase-3. The 2,7-dichlorofluorescein diacetate assay indicated that citreamicin ε substantially increased the intracellular concentration of reactive oxygen species (ROS). To confirm the hypothesis that citreamicin ε induced apoptosis through an increase in the intracellular ROS concentration, the oxidized products, oxicitreamicin ε A (3) and B (4), were obtained from a one-step reaction catalyzed by Ag 2O. These products, with a reduced capacity to increase the intracellular ROS concentration, exhibited a significantly weakened cytotoxicity in both HeLa and HepG2 cells compared with that of citreamicin ε A (1) and B (2). © 2013 American Chemical Society.
SponsorsThis work was supported by a research grant (DY125-15-T-02) from the China Ocean Mineral Resources Research and Development Association and by Grant SA-C0040/UK-C001 from King Abdullah University of Science and Technology (KAUST) to P.-Y.Q,
PublisherAmerican Chemical Society (ACS)
JournalChemical Research in Toxicology
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