Journal
CANCER LETTERS
Volume 366, Issue 1, Pages 100-111Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2015.06.008
Keywords
Genistein; Radioprotective; Apoptosis; DNA damage; Chromosome aberrations
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Funding
- National Natural Science Foundation of China [30972460, 81102123, 81272478]
- Shanghai Pujiang Outstanding Young Scientist Project [2012PJ-D-008]
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Radiation induced normal tissue damage is the most important limitation for the delivery of a high potentially curative radiation dose. Genistein (GEN), one of the main soy isoflavone components, has drawn wide attention for its bioactivity in alleviating radiation damage. However, the effects and molecular mechanisms underlying the radioprotective effects of GEN remain unclear. In the present study, we showed that low concentration of GEN (1.5 mu M) protected L-02 cells against radiation damage via inhibition of apoptosis, alleviation of DNA damage and chromosome aberration, down-regulation of GRP78 and up-regulation of HERP, HUS1 and hHR23A. In contrast, high concentration of GEN (20 mu M) demonstrated radiosensitizing characteristics through the promotion of apoptosis and chromosome aberration, impairment of DNA repair, up-regulation of GRP78, and down-regulation of HUS1, SIRT1, RAD17, RAD51 and RNF8. These findings shed light on using low, but not high-concentration GEN, as a potential candidate for adjuvant therapy to alleviate radiation-induced injuries to human recipients of ionizing radiation. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
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