title: Hydroquinone-induced malignant transformation of TK6 cells by facilitating SIRT1-mediated p53 degradation and up-regulating KRAS.
abstract: 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 HQ led 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 γ-H2AX. Furthermore, chronic HQ-treated (20μM 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.
authors: School of Public Health, Guangdong Medical University, PR-523808 Dongguan, Guangdong, China; Dongguan Key Laboratory of Enviromental Medicine, PR-523808 Dongguan, Guangdong, China.
authors: Yuting
authors: Y
authors: Chen
authors: School of Public Health, Guangdong Medical University, PR-523808 Dongguan, Guangdong, China; Dongguan Key Laboratory of Enviromental Medicine, PR-523808 Dongguan, Guangdong, China.
authors: Jiajia
authors: J
authors: Chen
authors: School of Public Health, Guangdong Medical University, PR-523808 Dongguan, Guangdong, China; Dongguan Key Laboratory of Enviromental Medicine, PR-523808 Dongguan, Guangdong, China.
authors: Lin
authors: L
authors: Yun
authors: School of Public Health, Guangdong Medical University, PR-523808 Dongguan, Guangdong, China; Dongguan Key Laboratory of Enviromental Medicine, PR-523808 Dongguan, Guangdong, China.
authors: Longmei
authors: L
authors: Xu
authors: School of Public Health, Guangdong Medical University, PR-523808 Dongguan, Guangdong, China; Dongguan Key Laboratory of Enviromental Medicine, PR-523808 Dongguan, Guangdong, China.
authors: Jiaxian
authors: J
authors: Liu
authors: School of Public Health, Guangdong Medical University, PR-523808 Dongguan, Guangdong, China; Dongguan Key Laboratory of Enviromental Medicine, PR-523808 Dongguan, Guangdong, China.
authors: Yongchun
authors: Y
authors: Xu
authors: School of Public Health, Guangdong Medical University, PR-523808 Dongguan, Guangdong, China; Dongguan Key Laboratory of Enviromental Medicine, PR-523808 Dongguan, Guangdong, China.
authors: Hui
authors: H
authors: Yang
authors: School of Public Health, Guangdong Medical University, PR-523808 Dongguan, Guangdong, China; Dongguan Key Laboratory of Enviromental Medicine, PR-523808 Dongguan, Guangdong, China.
authors: Hairong
authors: H
authors: Liang
authors: School of Public Health, Guangdong Medical University, PR-523808 Dongguan, Guangdong, China; Dongguan Key Laboratory of Enviromental Medicine, PR-523808 Dongguan, Guangdong, China. Electronic address: thw@gdmu.edu.cn.
authors: Huanwen
authors: H
authors: Tang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000633:toxicity; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D006873:Hydroquinones / Q000633:toxicity*; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D000975:Antioxidants; D006873:Hydroquinones; C117307:KRAS protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D016283:Proto-Oncogene Proteins p21(ras); C031927:hydroquinone
keywords: Hydroquinone; KRAS; Leukemia; Malignant transformation; SIRT1; p53