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Radiosensitization by celastrol is mediated by modification of antioxidant thiol molecules

Title
Radiosensitization by celastrol is mediated by modification of antioxidant thiol molecules
Authors
Seo H.R.Seo W.D.Pyun B.-J.Lee B.W.Jin Y.B.Park K.H.Seo E.-K.Lee Y.-J.Lee Y.-S.
Ewha Authors
서은경이윤실
SCOPUS Author ID
서은경scopus; 이윤실scopus
Issue Date
2011
Journal Title
Chemico-Biological Interactions
ISSN
0009-2797JCR Link
Citation
vol. 193, no. 1, pp. 34 - 42
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
The radiosensitizing effects of naturally occurring triterpenes were investigated in human lung cancer cells. Several quinone methide-containing triterpenes (QMTs) enhanced the cytotoxic effect of ionizing radiation (IR) and of these QMTs, celastrol (CE) had the greatest enhancing effect on IR-induced cell death in vitro. Additionally, the quinone methide moiety of CE was shown to be essential for CE-mediated radiosensitization; in contrast, dihydrocelastrol (DHCE), does not contain this moiety. Reactive oxygen species (ROS) production by IR was augmented in combination with CE, which was responsible for CE-mediated radiosensitization. CE induced the thiol reactivity and inhibited the activities of antioxidant molecules, such as thioredoxin reductase and glutathione. In vivo, nude mouse xenografting data also revealed that tumor growth delay was greater in mice treated with CE plus IR, compared with those treated with CE or IR alone. When DHCE, instead of CE, was combined with IR, tumor growth delay was similar to that in IR alone-treated mice. These results demonstrate that CE synergistically enhances the effects of IR and suggest the novel anticancer therapeutic use of CE in combination with radiation therapy. © 2011 Elsevier Ireland Ltd. All rights reserved.
DOI
10.1016/j.cbi.2011.04.009
Appears in Collections:
약학대학 > 약학과 > Journal papers
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