Liu 2016 Apoptosis

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Liu X, Gao RW, Li M, Si CF, He YP, Wang M, Yang Y, Zheng QY, Wang CY (2016) The ROS derived mitochondrial respiration not from NADPH oxidase plays key role in Celastrol against angiotensin II-mediated HepG2 cell proliferation. Apoptosis 21:1315-26.

» PMID: 27658784

Liu X, Gao RW, Li M, Si CF, He YP, Wang M, Yang Y, Zheng QY, Wang CY (2016) Apoptosis

Abstract: Angiotensin II (AngII) is an important factor that promotes the proliferation of cancer cells, whereas celastrol exhibits a significant antitumor activity in various cancer models. Whether celastrol can effectively suppress AngII mediated cell proliferation remains unknown. In this study, we studied the effect of celastrol on AngII-induced HepG2 cell proliferation and evaluated its underlying mechanism. The results revealed that AngII was able to significantly promote HepG2 cell proliferation via up-regulating AngII type 1 (AT1) receptor expression, improving mitochondrial respiratory function, enhancing nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, increasing the levels of reactive oxygen species (ROS) and pro-inflammatory cytokines. The excess ROS from mitochondrial dysfunction is able to cause the apoptosis of tumor cells via activating caspase3 signal pathway. In addition, the reaction between NO and ROS results in the formation of peroxynitrite (ONOO-), and then promoting cell damage. Celastrol dramatically enhanced ROS generation, thereby causing cell apoptosis through inhibiting mitochodrial respiratory function and boosting the expression levels of AngII type 2 (AT2) receptor without influencing NADPH oxidase activity. PD123319 as a special inhibitor of AT2R was able to effectively decrease the levels of inflammatory cytokines and endothelial nitric oxide synthase (eNOS) activity, but only partially attenuate the effect of celastrol on AnII mediated HepG2 cell proliferation. Thus, celastrol has the potential for use in liver cancer therapy. ROS derived from mitochondrial is an important factor for celastrol to suppress HepG2 cell proliferation.

Keywords: Angiotensin II, Angiotensin II type 2 receptor, Apoptosis, Celastrol, Mitochondrial function, NADPH oxidase, HepG2


Labels: MiParea: Respiration, Pharmacology;toxicology  Pathology: Cancer  Stress:Oxidative stress;RONS  Organism: Human  Tissue;cell: Liver, Other cell lines  Preparation: Intact cells 


Coupling state: ROUTINE 

HRR: Oxygraph-2k 

2016-11