| Induction of ROS formation, poly(ADP-ribose) polymerase-1 activation, and cell death by PCB126 and PCB153 in human T47D and MDA-MB-231 breast cancer cells. | |
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MedLine Citation:
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PMID: 16884709 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The primary purpose of this research is to investigate whether exposure to polychlorinated biphenyls (PCBs), i.e. PCB153 and PCB126, is associated with induction of reactive oxygen species (ROS), poly(ADP-ribose) polymerase-1 (PARP-1) activation, and cell death in human T47D and MDA-MB-231 breast cancer cells. Results indicated that PCB153 and PCB126 induced concentration- and time-dependent increases in cytotoxic response and ROS formation in both T47D and MDA-MB-231 cells. At non-cytotoxic concentrations both PCB153 and PCB126 induced decreases in intracellular NAD(P)H and NAD+ in T47D and MDA-MB-231 cells where T47D cells were more resistant to PCB-induced reduction in intracellular NAD(P)H than MDA-MB-231 cells. Further investigation indicated that three specific PARP inhibitors completely blocked PCB-induced decreases in intracellular NAD(P)H in both T47D and MDA-MB-231 cells. These results imply that decreases in intracellular NAD(P)H in PCB-treated cells may be, in part, due to depletion of intracellular NAD+ pool mediated by PARP-1 activation through formation of DNA strand breaks. Overall, the extent of cytotoxic response, ROS formation, and PARP-1 activation generated in T47D and MDA-MB-231 cells was greater for PCB153 than for PCB126. In addition, the cytotoxicity induced by PCB153 and PCB126 in both T47D and MDA-MB-231 cells was completely blocked by co-treatment of catalase, dimethylsulfoxide, cupper (I)-/iron (II)-specific chelators, and CYP1A/2B inhibitors. This evidence suggests the involvement of ROS, Cu(I), Fe(II), and CYP1A/2B enzymes in mediating the induction of cell death by PCB153 and PCB126. Further, antagonism was observed between PCB126 and PCB153 for effects on cytotoxic response and ROS formation in T47D and MDA-MB-231 cells. Antagonism was also observed between PCB153 and PCB126 in the induction of NAD(P)H depletion at lower concentration (<10 microM) in T47D cells, but not in MDA-MB-231 cells. In conclusions, results from our investigation suggest that ROS formation induced by PCBs is a significant determinant factor in mediating the DNA damage and cell death in human breast cancer cells. The data also suggests that the status of estrogen receptor alpha may play a role in modulating the PCB-induced oxidative DNA damage and cell death in human breast cancer cells. |
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Authors:
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Chia-Hua Lin; Po-Hsiung Lin |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2006-07-01 |
Journal Detail:
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Title: Chemico-biological interactions Volume: 162 ISSN: 0009-2797 ISO Abbreviation: Chem. Biol. Interact. Publication Date: 2006 Aug |
Date Detail:
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Created Date: 2006-08-16 Completed Date: 2006-10-30 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0227276 Medline TA: Chem Biol Interact Country: Ireland |
Other Details:
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Languages: eng Pagination: 181-94 Citation Subset: IM |
Affiliation:
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Department of Environmental Engineering, National Chung Hsing University, Taichung, Taiwan, ROC. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Benzoflavones
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pharmacology Breast Neoplasms / metabolism, pathology Catalase / pharmacology Cell Line, Tumor Cell Survival / drug effects Chelating Agents / pharmacology Cytochrome P-450 Enzyme System / antagonists & inhibitors Dimethyl Sulfoxide / pharmacology Dose-Response Relationship, Drug Enzyme Activation / drug effects Enzyme Inhibitors / pharmacology Female Fluoresceins / chemistry Humans Metyrapone / pharmacology Molecular Structure NAD / metabolism NADP / metabolism Oxidation-Reduction / drug effects Poly(ADP-ribose) Polymerases / antagonists & inhibitors, metabolism* Polychlorinated Biphenyls / chemistry, pharmacology* Reactive Oxygen Species / metabolism* Tamoxifen / analogs & derivatives, pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Benzoflavones; 0/Chelating Agents; 0/Enzyme Inhibitors; 0/Fluoresceins; 0/Polychlorinated Biphenyls; 0/Reactive Oxygen Species; 10540-29-1/Tamoxifen; 2044-85-1/diacetyldichlorofluorescein; 35065-27-1/2,4,5,2',4',5'-hexachlorobiphenyl; 53-59-8/NADP; 53-84-9/NAD; 54-36-4/Metyrapone; 57465-28-8/3,4,5,3',4'-pentachlorobiphenyl; 604-59-1/alpha-naphthoflavone; 67-68-5/Dimethyl Sulfoxide; 68392-35-8/4-hydroxytamoxifen; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.11.1.6/Catalase; EC 2.4.2.30/PARP1 protein, human; EC 2.4.2.30/Poly(ADP-ribose) Polymerases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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