Possible aryl hydrocarbon receptor-independent pathway of 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced antiproliferative response in human breast cancer cells |
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Authors: | Yoshioka Hiroki Hiromori Youhei Aoki Akira Kimura Tomoki Fujii-Kuriyama Yoshiaki Nagase Hisamitsu Nakanishi Tsuyoshi |
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Affiliation: | Laboratory of Hygienic Chemistry and Molecular Toxicology, Gifu Pharmaceutical University, 1-25-4 Daigaku-Nishi, Gifu, Gifu 501-1196, Japan. |
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Abstract: | 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a ligand with high affinity for the aryl hydrocarbon receptor (AhR). It suppresses 17β-estradiol (E2)-induced cell proliferation in human breast cancer cells. Although it has been theorized that the AhR is involved in TCDD-induced antiestrogenic activity and antiproliferation in human breast cancer cells, some evidence suggests that these activities of chlorinated aromatic compounds also occur by AhR-independent pathways. Here, we investigated the possibility of TCDD-induced antiproliferative responses in human breast cancer cells through AhR-independent pathways. Compared with that in vehicle-treated controls, DNA synthesis was significantly suppressed in MCF-7 cells and ZR75-1 cells treated with TCDD at a very low concentration (0.01 nM), whereas that in human ovarian carcinoma OVCAR3 cells, human cervical carcinoma HeLa cells and human choriocarcinoma JEG-3 cells was unaffected, even by exposure to 10 nM TCDD. The suppression induced by TCDD was not associated with the estrogen receptor α-signaling pathway. Another AhR agonist, 3,3',4,4',5-pentachlorobiphenyl, had no effect on DNA synthesis in MCF-7 cells at concentrations high enough to induce the transactivation function of the AhR. Furthermore, in MCF-7 cells, knockdown of the AhR by RNA interference had no effect on TCDD-induced antiproliferation. These findings suggest that the principal pathways of TCDD-induced antiproliferation in breast cancer cells are not AhR dependent. |
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Keywords: | 3MC, 3-methylcholanthrene AhR, aryl hydrocarbon receptor ARNT, aryl hydrocarbon nuclear translocator ATCC, American Type Culture Collection DMEM, Dulbecco's modified Eagle's medium FCS, fetal calf serum LUC, luciferase MEM, minimal essential medium PCB126, 3,3′4,4′,5-pentachlorobiphenyl PCR, polymerase chain reaction TCDD, 2,3,7,8-tetrachlorodibenzo-p-dioxin XRE, xenobiotic-responsive element |
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