Caspase-3-dependent apoptosis of citreamicin ε-induced heLa iells Is associated with reactive oxygen species generation

Handle URI:
http://hdl.handle.net/10754/562863
Title:
Caspase-3-dependent apoptosis of citreamicin ε-induced heLa iells Is associated with reactive oxygen species generation
Authors:
Liu, Lingli; He, Lisheng; Xü, Ying; Han, Zhuang; Li, Yongxin; Zhong, Jialiang; Guo, Xianrong; Zhang, Xixiang ( 0000-0002-3478-6414 ) ; Ko, Kamming; Qian, Peiyuan
Abstract:
Citreamicins, 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.
KAUST Department:
Advanced Nanofabrication, Imaging and Characterization Core Lab; Physical Sciences and Engineering (PSE) Division; Materials Science and Engineering Program
Publisher:
American Chemical Society (ACS)
Journal:
Chemical Research in Toxicology
Issue Date:
15-Jul-2013
DOI:
10.1021/tx4000304
PubMed ID:
23745985
Type:
Article
ISSN:
0893228X
Sponsors:
This 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,
Is Supplemented By:
Liu, L.-L., He, L.-S., Xu, Y., Han, Z., Li, Y.-X., Zhong, J.-L., … Qian, P.-Y. (2015). CCDC 890247: Experimental Crystal Structure Determination [Data set]. Cambridge Crystallographic Data Centre. https://doi.org/10.5517/ccywcnt; DOI:10.5517/ccywcnt; HANDLE:http://hdl.handle.net/10754/624728
Appears in Collections:
Articles; Advanced Nanofabrication, Imaging and Characterization Core Lab; Physical Sciences and Engineering (PSE) Division; Materials Science and Engineering Program

Full metadata record

DC FieldValue Language
dc.contributor.authorLiu, Linglien
dc.contributor.authorHe, Lishengen
dc.contributor.authorXü, Yingen
dc.contributor.authorHan, Zhuangen
dc.contributor.authorLi, Yongxinen
dc.contributor.authorZhong, Jialiangen
dc.contributor.authorGuo, Xianrongen
dc.contributor.authorZhang, Xixiangen
dc.contributor.authorKo, Kammingen
dc.contributor.authorQian, Peiyuanen
dc.date.accessioned2015-08-03T11:13:14Zen
dc.date.available2015-08-03T11:13:14Zen
dc.date.issued2013-07-15en
dc.identifier.issn0893228Xen
dc.identifier.pmid23745985en
dc.identifier.doi10.1021/tx4000304en
dc.identifier.urihttp://hdl.handle.net/10754/562863en
dc.description.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.en
dc.description.sponsorshipThis 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,en
dc.publisherAmerican Chemical Society (ACS)en
dc.titleCaspase-3-dependent apoptosis of citreamicin ε-induced heLa iells Is associated with reactive oxygen species generationen
dc.typeArticleen
dc.contributor.departmentAdvanced Nanofabrication, Imaging and Characterization Core Laben
dc.contributor.departmentPhysical Sciences and Engineering (PSE) Divisionen
dc.contributor.departmentMaterials Science and Engineering Programen
dc.identifier.journalChemical Research in Toxicologyen
dc.contributor.institutionDivision of Life Science, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kongen
dc.contributor.institutionShanghai Institute of Pharmaceutical Industry, Shanghai 200040, Chinaen
kaust.authorZhang, Xixiangen
kaust.authorGuo, Xianrongen
dc.relation.isSupplementedByLiu, L.-L., He, L.-S., Xu, Y., Han, Z., Li, Y.-X., Zhong, J.-L., … Qian, P.-Y. (2015). CCDC 890247: Experimental Crystal Structure Determination [Data set]. Cambridge Crystallographic Data Centre. https://doi.org/10.5517/ccywcnten
dc.relation.isSupplementedByDOI:10.5517/ccywcnten
dc.relation.isSupplementedByHANDLE:http://hdl.handle.net/10754/624728en

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