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
文献类型：期刊论文
| 作者 | Sheng, Zhi-Guo; Shen, Chen; Fan, Rui-Mei; Chao, Xi-Juan; Liu, Yu-Xiang; Zhu, Ben-Zhan |
| 刊名 | TOXICOLOGICAL SCIENCES
 |
| 出版日期 | 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. |
| 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.Xinjiang Normal Univ, Coll Chem & Chem Engn, Urumqi 830054, Xinjiang, Peoples R China 2.Chinese Acad Sci, Res Ctr Ecoenvironm Sci, Beijing 100085, 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. |
入库方式： OAI收割
来源：生态环境研究中心
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