Journal
TOXICOLOGY LETTERS
Volume 259, Issue -, Pages 133-142Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.toxlet.2016.08.006
Keywords
Hydroquinone; SIRT1; Malignant transformation; p53; KRAS; Leukemia
Categories
Funding
- National Natural Science Foundation of China [81273116]
- Guangdong Provincial Natural Science Foundation, China [S2013010015153]
- Key project of Science and Technology Program of Dongguan Bureau of Science and Technology, China [2012108101011]
- Science and Technology Program of Zhanjiang Bureau of Science and Technology, China [2013B01082]
- Science Foundation of Guangdong Medical University, China [M2013004]
- Key Program of National Natural Science Foundation of China [81430079]
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Hydroquinone (HQ), known as one of the metabolic products of benzene, causes a number of hematologic malignancies. The study evaluated the potential mechanism of Sirtuin 1 (SIRT1) in HQ-induced TK6 cell malignant transformation. The data of our study show that short term exposure of TK6 cells to HQled to a decrease expression of SIRT1. Knockdown of SIRT1 sensitized to the HQ-induced apoptosis in vitro and increased the expression of p53, p21 and gamma-H2AX. Furthermore, chronic HQ-treated (20 mu M once a week for 19 weeks) caused carcinogenic transformation and was confirmed by abnormal cell proliferation, matrix metalloproteinase 9(MMP9) and subcutaneous tumor formation in nude mice. SIRT1 increased KRAS expression, and decreased H3K9 and H3K18 acetylation, inhibited p53 signaling and the level of caspase-3 in HQ-induced transformation cells. Taken together, these data suggest that SIRT1 is involved in HQ-induced malignant transformation associated with suppressing p53 signaling and activation of KRAS. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
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