期刊
ONCOLOGY LETTERS
卷 7, 期 6, 页码 1812-1818出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/ol.2014.2018
关键词
shikonin; beta,beta-dimethylacrylshikonin; radiosensitizer; reactive oxygen species; apoptosis
类别
资金
- Nuclear Research and Development Program [NRF-2010-0018713]
- Basic Science Research Program through the National Research Foundation of Korea - Ministry of Education, Science and Technology [NRF-2011-0007381]
Shikonin, a naphthoquinone derivative, has been shown to possess antitumor activity. In the present study, the effects of shikonin and its analog, beta,beta-dimethylacrylshikonin, were investigated as radiosensitizers on the human colon cancer cell line, HCT-116. Shikonin and, to a greater extent, its analog-induced apoptosis of HCT-116 cells further synergistically potentiated the induction of apoptosis when combined with ionizing radiation (IR) treatment. Shikonins also stimulated an increase in reactive oxygen species (ROS) production and IR-induced DNA damage. Pre-treatment with the ROS scavenger, N-acetylcysteine, suppressed the enhancement of IR-induced DNA damage and apoptosis stimulated by shikonins, indicating that shikonins exert their radiosensitizing effects through ROS upregulation. The radiosensitizing effect of shikonins was also examined in vivo using the xenograft mouse model. Consistent with the in vitro results, injection of beta,beta-dimethylacrylshikonin combined with IR treatment significantly suppressed tumor growth of the HCT-116 xenograft. Taken together, the results show that beta,beta-dimethylacrylshikonin is a promising agent for developing an improved strategy for radiotherapy against tumors.
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