The Critical Role of X Chromosome-Linked Inhibitor of Apoptosis (XIAP) in Differential Synergism Induced by Pentachlorophenol and Copper-1,10-Phenanthroline Complex in Normal and Cancer Liver Cells

CORC > 生态环境研究中心 > 中国科学院生态环境研究中心 > 环境化学与生态毒理学国家重点实验室

	The Critical Role of X Chromosome-Linked Inhibitor of Apoptosis (XIAP) in Differential Synergism Induced by Pentachlorophenol and Copper-1,10-Phenanthroline Complex in Normal and Cancer Liver Cells
	Sheng, Zhi-Guo ; Shen, Chen ; Fan, Rui-Mei ; Chao, Xi-Juan ; Liu, Yu-Xiang ; Zhu, Ben-Zhan
刊名	TOXICOLOGICAL SCIENCES
	2019-04
卷号	168 期号:2 页码:339-348
关键词	pentachlorophenol copper-1 10-phenanthroline synergistic cytotoxicity toxicity difference XIAP
ISSN号	1096-6080
英文摘要	Chemical pollutants often co-occur and can interact to cause unexpected combined toxic effects. Both pentachlorophenol (PCP) and copper-1,10-phenanthroline [Cu(OP)(2)], used as wood preservatives, coexist in fluids and tissues of ordinary population. Our previous studies demonstrate that a combination of subtoxic PCP and Cu(OP)(2) causes synergistic toxicity on Escherichia coli and hepatocarcinoma cells. However, it is not clear whether this effect also occurs in normal hepatocytes; and if so, what are the differences as compared with the hepatocarcinoma cells. We demonstrate that the combination of low-toxic PCP and Cu(OP)(2) (0-1.6 mu M; PCP/Cu(OP)(2) molar ratio: 2:1) induces a concentration-dependent intracellular copper accumulation, apoptosis, caspase-3/9 activation, depolarization of mitochondrial membrane potential, and oxidative stress (reactive oxygen species increasing and glutathione/oxidized glutathione ratio decreasing) in both normal hepatocytes HL-7702 and hepatocarcinoma HepG2 cells. However, HepG2 cells are more susceptible to the above molecular events as compared with HL-7702 cells. Further data reveal that PCP/Cu(OP)(2) markedly decreases X chromosome-linked inhibitor of apoptosis (XIAP), p-ERK-1/2, and p-JNK protein expression in HepG2, but not HL-7702. Overexpression of XIAP gene in HepG2 significantly blocks PCP/Cu(OP)(2)-induced cytotoxicity, caspase activity, apoptosis, ROS accumulation, and antioxidant genes expression. These results suggest that the combination of low-toxic PCP and Cu(OP)(2) preferentially induce synergistic cytotoxicity in human hepatocarcinoma cells by XIAP-ROS-apoptosis pathway, compared with the normal hepatocytes. The present data not only confirm the synergistic toxicity of PCP/Cu(OP)(2) combination in normal liver cells, but also suggest a possible opportunity in developing new therapeutic approaches for liver cancer by sensitizing cancer cells to chemotherapy.
内容类型	期刊论文
源URL	[http://ir.rcees.ac.cn/handle/311016/43037]
专题	生态环境研究中心_环境化学与生态毒理学国家重点实验室
作者单位	1.Chinese Acad Sci, Res Ctr Ecoenvironm Sci, Beijing 100085, Peoples R China 2.Xinjiang Normal Univ, Coll Chem & Chem Engn, Urumqi 830054, Xinjiang, Peoples R China 3.Oregon State Univ, Linus Pauling Inst, Corvallis, OR 97331 USA
推荐引用方式 GB/T 7714	Sheng, Zhi-Guo,Shen, Chen,Fan, Rui-Mei,et al. The Critical Role of X Chromosome-Linked Inhibitor of Apoptosis (XIAP) in Differential Synergism Induced by Pentachlorophenol and Copper-1,10-Phenanthroline Complex in Normal and Cancer Liver Cells[J]. TOXICOLOGICAL SCIENCES,2019,168(2):339-348.
APA	Sheng, Zhi-Guo,Shen, Chen,Fan, Rui-Mei,Chao, Xi-Juan,Liu, Yu-Xiang,&Zhu, Ben-Zhan.(2019).The Critical Role of X Chromosome-Linked Inhibitor of Apoptosis (XIAP) in Differential Synergism Induced by Pentachlorophenol and Copper-1,10-Phenanthroline Complex in Normal and Cancer Liver Cells.TOXICOLOGICAL SCIENCES,168(2),339-348.
MLA	Sheng, Zhi-Guo,et al."The Critical Role of X Chromosome-Linked Inhibitor of Apoptosis (XIAP) in Differential Synergism Induced by Pentachlorophenol and Copper-1,10-Phenanthroline Complex in Normal and Cancer Liver Cells".TOXICOLOGICAL SCIENCES 168.2(2019):339-348.