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ATOX1 gene silencing increases susceptibility to anticancer therapy based on copper ionophores or chelating drugs.
- Source :
-
Journal of Inorganic Biochemistry . Mar2016, Vol. 156, p145-152. 8p. - Publication Year :
- 2016
-
Abstract
- Copper is a catalytic cofactor required for the normal function of many enzymes involved in fundamental biological processes but highly cytotoxic when in excess. Therefore its homeostasis and distribution is strictly regulated by a network of transporters and intracellular chaperones. ATOX1 (antioxidant protein 1) is a copper chaperone that plays a role in copper homeostasis by binding and transporting cytosolic copper to ATPase proteins in the trans -Golgi network. In the present study the Caco-2 cell line, a colon carcinoma cell line, was used as an in vitro model to evaluate if ATOX1 deficiency could affect sensitivity to experimentally induced copper dyshomeostasis. Silencing of ATOX1 increased toxicity of a short treatment with a high concentration of Cu 2 + . Copper ionophores, such as 5-chloro-8-hydroxyquinoline, induced a copper-dependent cell toxicity which was significantly potentiated after ATOX1 silencing. The copper chelator TPEN (N,N,N′,N′-tetrakis (2-pyridylmethyl) ethylenediamine) produced a form of cell toxicity that was reversed by the addition of Cu 2 + . ATOX1 silencing increased Caco-2 cell sensitivity to TPEN toxicity. Our results suggest the possibility of a therapy with copper-chelating or ionophore drugs in subtypes of tumors showing specific alterations in ATOX1 expression. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01620134
- Volume :
- 156
- Database :
- Academic Search Index
- Journal :
- Journal of Inorganic Biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 112828146
- Full Text :
- https://doi.org/10.1016/j.jinorgbio.2016.01.002