TBBPA rather than its main derivatives enhanced growth of endometrial cancer via p53 ubiquitination  

作　　者：Hongyan Yu Jingxu Zhang Jing Liu Ruonan Pan Yu Wang Xiaoting Jin Rifat Zubair Ahmed Yuxin Zheng 

机构地区：[1]Department of Occupational Health and Environmental Health,School of Public Health,Qingdao University,Qingdao 266071,China [2]State Key Laboratory of Environmental Chemistry and Ecotoxicology,Research Center for Eco-Environmental Sciences,Chinese Academy of Sciences,Beijing 100085,China [3]Department of Genetics,University of Karachi,Karachi 75270,Pakistan

出　　处：《Journal of Environmental Sciences》2024年第3期82-95,共14页环境科学学报（英文版）

基　　金：supported by the Taishan Scholars Program of Shandong Province (No.tsqn201909101);the National Natural Science Foundation of China (Nos.21976114,92043202 and 91943301)。

摘　　要：Tetrabromobisphenol A(TBBPA)and its derivatives widely exist in various environments and biota.Although the available data indicate that TBBPA exposure is highly associated with the increased incidence of endometrial cancer(EC),the effects of TBBPA and its main derivatives on EC proliferation and the involved crucial mechanism remain unclear.The present study aimed to investigate the effects of TBBPA and its derivatives under environmental concentrations on the proliferation of EC,and the crucial mechanism on the progression of EC caused by bromine fame retardants exposure.In this research,TBBPA and two of the most common TBBPA derivatives including TBBPA bis(2-hydroxyethyl ether)(TBBPABHEE)and TBBPA bis(dibromopropyl ether)(TBBPA-BDBPE)were screened for their capacities in induced EC proliferation and explored the related mechanism by in vitro cell culture model and in vivo mice model.Under environmental concentrations,TBBPA promoted the proliferation of EC,the main derivatives of TBBPA(TBBPA-BHEE and TBBPA-BDBPE)did not present the similar facilitation effects.The ubiquitination degradation of p53 was crucial in TBBPA induced EC proliferation,which resulted in the increase of downstream cell cycle and decrease of apoptosis.The further molecular docking result suggested the high affinity between TBBPA and ubiquitinated proteasome.This finding revealed the effects of TBBPA and its derivatives on EC proliferation,thus providing novel insights into the underlying mechanisms of TBBPA-caused EC.

关 键 词：Tetrabromobisphenol A(TBBPA) Endometrial cancer(EC) DERIVATIVES Ubiquitin proteases P53 

分 类 号：R737.33[医药卫生—肿瘤] X503.1[医药卫生—临床医学]