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Title: P21(Waf1/Cip1) plays a critical role in furazolidone-induced apoptosis in HepG2 cells through influencing the caspase-3 activation and ROS generation. Author: Deng S, Tang S, Dai C, Zhou Y, Yang X, Li D, Xiao X. Journal: Food Chem Toxicol; 2016 Feb; 88():1-12. PubMed ID: 26687534. Abstract: Furazolidone (FZD), a synthetic nitrofuran with a broad spectrum of antimicrobial activities, has been shown to exhibit marked genotoxity and cytotoxicity in vitro, but the proper mechanism was unclear. P21(Waf1/Cip1) (p21), a cyclin-dependent kinase, is critically involved in cell cycle arrest and apoptosis in response to DNA injury. This study was aimed to explore the role of p21 in FZD-induced apoptosis in HepG2 cells and uncover its possible mechanism. Firstly, we demonstrated that FZD (50 μg/mL) treatment increased the mRNA level of p21 but reduced the protein level of p21 by shortening its half-life. Moreover, the degradation of p21 was associated with the inhibition of PI3K/Akt pathway by FZD. Then, the change of p21 protein expression modulated FZD-induced apoptosis. Overexpression of p21 attenuated FZD-induced caspase-3 activation and ROS generation, eventually reduced apoptosis. Conversely, knockdown of p21 by siRNA enhanced FZD-induced those phenomenon. In addition, the influence of p21 on FZD-induced ROS generation might be associated with Nrf2/HO-1 pathway which was a key regulator in defense response against oxidative stress. In conclusion, these findings demonstrated that p21 plays a critical role in FZD-induced apoptosis in HepG2 cells through influencing the caspase-3 activation and ROS generation.[Abstract] [Full Text] [Related] [New Search]