Zinc at Sub-Cytotoxic Concentrations Induces Heme Oxygenase-1 Expression in Human Cancer Cells
| Autor: | Jing Xue, Shuai Wang, Jinchang Wu, Bethany N. Hannafon, Wei-Qun Ding |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: | |
| Zdroj: | Cellular Physiology and Biochemistry, Vol 32, Iss 1, Pp 100-110 (2013) |
| Druh dokumentu: | article |
| ISSN: | 1015-8987 1421-9778 |
| DOI: | 10.1159/000350128 |
| Popis: | Background/Aims: This study investigated the effects of zinc on heme oxygenase-1 (HO-1) expression in human cancer cells. Methods/Results: Zinc at sub-cytotoxic concentrations (50-100 μM) induces HO-1 expression in the MDA-MB-231 (human breast cancer) and A2780 (human ovarian cancer) cell lines in a concentration- and time-dependent manner. The induction of HO-1 by zinc was detected after 4-6 hours of treatment, reached maximal level at 8 hours, and declined thereafter. Using a human HO-1 gene promoter reporter construct, we identified two antioxidant response elements (AREs) that mediated the zinc-induced increase in HO-1 gene transcription, indicating that the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling pathway is involved in this event. This assumption was supported by the observations that knockdown of Nrf2 expression compromised the zinc-induced increase in HO-1 gene transcription, and that zinc increased Nrf2 protein expression and the Nrf2 binding to the AREs. Additionally, we found that the zinc-induced HO-1 gene transcription can be enhanced by clioquinol, a zinc ionophore, and reversed by pretreatment with TPEN, a known zinc chelator, indicating that an increase in intracellular zinc levels is responsible for this induction. Conclusion: These findings demonstrate that zinc at sub-cytotoxic concentrations induces HO-1 expression in human cancer cells. The biological significance of this induction merits further investigation. |
| Databáze: | Directory of Open Access Journals |
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