Radiosensitization by celastrol is mediated by modification of antioxidant thiol molecules

Haeng Ran Seo, Woo Duck Seo, Bo Jeong Pyun, Byong Won Lee, Yeung Bae Jin, Ki Hun Park, Eun Kyoung Seo, Yoon Jin Lee, Yun Sil Lee

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

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.

Original languageEnglish
Pages (from-to)34-42
Number of pages9
JournalChemico-Biological Interactions
Volume193
Issue number1
DOIs
StatePublished - 15 Aug 2011

Keywords

  • Antioxidant
  • Celastrol
  • Radiosensitization
  • Reactive oxygen species

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