PARP-1 via regulation of p53 and p16, is involved in the hydroquinone-induced malignant transformation of TK6 cells by decelerating the cell cycle

Lu Zhai; Hairong Liang; Jinlin Du; Mingwei Sun; Weifeng Qiu; Huanwen Tang; Hao Luo

doi:10.1016/j.tiv.2021.105153

PARP-1 via regulation of p53 and p16, is involved in the hydroquinone-induced malignant transformation of TK6 cells by decelerating the cell cycle

Toxicol In Vitro. 2021 Aug:74:105153. doi: 10.1016/j.tiv.2021.105153. Epub 2021 Mar 24.

Authors

Lu Zhai¹, Hairong Liang¹, Jinlin Du¹, Mingwei Sun¹, Weifeng Qiu¹, Huanwen Tang², Hao Luo³

Affiliations

¹ Department of Environmental and Occupational Health, Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan, China.
² Department of Environmental and Occupational Health, Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan, China. Electronic address: thw@gdmu.edu.cn.
³ Department of Environmental and Occupational Health, Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan, China. Electronic address: lh426@gdmu.edu.cn.

PMID: 33771647
DOI: 10.1016/j.tiv.2021.105153

Abstract

Poly(ADP-ribose)polymerase-1 (PARP-1) plays a crucial role in DNA damage repair and could be viewed as both a tumor promoter and tumor-suppressor gene. However, the effects of PARP-1 in hydroquinone-induced malignant transformation of TK6 cells remain to be further elucidated. The present research evaluated the potential mechanism of PARP-1 in hydroquinone-induced malignant transformation of TK6 cells. The results indicated that high PARP-1 inhibited TK6 cells malignant transformation after chronic exposure to HQ. We further confirmed that PARP-1 overexpression blocked cell proliferation, and decelerated cell cycle progression in vitro and in vivo. The immunoblotting analysis indicated that PARP-1 regulated cell cycle progression via p16/Rb and p53. Therefore, we conclude that PARP-1 is involved in HQ-induced malignant transformation associated with increasing p16/Rb and p53 which resulting in decelerating the cell cycle progression.

Keywords: Cell cycle; Hydroquinone; Malignant transformation; PARP-1; p16; p53.

MeSH terms

Animals
Cell Cycle / drug effects
Cell Line
Cell Movement / drug effects
Cell Proliferation / drug effects
Cell Transformation, Neoplastic / chemically induced
Cell Transformation, Neoplastic / genetics*
Cyclin-Dependent Kinase Inhibitor p16 / metabolism*
Humans
Hydroquinones / toxicity*
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Poly (ADP-Ribose) Polymerase-1 / genetics*
Poly (ADP-Ribose) Polymerase-1 / metabolism
Proto-Oncogene Proteins c-bcl-2 / metabolism
Signal Transduction / drug effects
Tumor Suppressor Protein p53 / metabolism*

Substances

BCL2 protein, human
CDKN2A protein, human
Cyclin-Dependent Kinase Inhibitor p16
Hydroquinones
Proto-Oncogene Proteins c-bcl-2
Tumor Suppressor Protein p53
PARP1 protein, human
Poly (ADP-Ribose) Polymerase-1
hydroquinone