Hydroquinone-induced malignant transformation of TK6 cells by facilitating SIRT1-mediated p53 degradation and up-regulating KRAS. (30th September 2016)

• Record Type: Journal Article
• Authors: Chen, Yuting; Chen, Jiajia; Yun, Lin; Xu, Longmei; Liu, Jiaxian; Xu, Yongchun; Yang, Hui; Liang, Hairong; Tang, Huanwen
• Is Part Of: Toxicology letters. Volume 259(2016)
• Page Start: 133
• Page End: 142
• Publication Date: 2016-09-30
• Subjects: HQ hydroquinone -- SIRT1 Sirtuin 1 -- MMP9 matrix metalloproteinase 9 -- HDACs histone deacetylases -- NAD+ nicotinamide adenine dinucleotide -- acH3 acetylated histone H3 -- shRNA small hairpin RNA -- FITC fluorescein isothiocyanate -- PI3K phosphatidylinositol 3 kinase -- PARP-1 poly(ADP-ribose) polymerase-1 -- AML acute myeloid leukemia -- B[a]P benzo(a)pyrene; Hydroquinone -- SIRT1 -- Malignant transformation -- p53 -- KRAS -- Leukemia; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2016.08.006
• Languages: English
• ISSNs: 0378-4274

Abstract

Graphical abstract: Highlights: SIRT1 silencing promotes apoptosis after hydroquinone (HQ) treatment and associated p53 activation. Chronic HQ exposure causes TK6 cells malignant transformation and tumorigenesis. SIRT1 mediates KRAS activation and p53 signaling deactivation contributed to HQ-induced malignant transformation in TK6 cells. 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 (20 μM 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.