Radiosensitization by celastrol is mediated by modification of antioxidant thiol molecules |
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Authors: | Seo Haeng Ran Seo Woo Duck Pyun Bo-Jeong Lee Byong Won Jin Yeung Bae Park Ki Hun Seo Eun-Kyoung Lee Yoon-Jin Lee Yun-Sil |
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Institution: | aDivision of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, Republic of Korea;bDepartment of Functional Crop, National Institute of Crop Science, Rural Development Administration, Miryang 627-803, Republic of Korea;cCollege of Pharmacy and Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750, Republic of Korea;dDivision of Applied Life Science (BK21 Program), EB-NCRC, Institute of Agriculture and Life Science, Gyeongsang National University, Jinju 660-701, Republic of Korea |
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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. |
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Keywords: | Celastrol Reactive oxygen species Antioxidant Radiosensitization |
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