Browsing by Author "Ludwig, Andreas"

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    Etoposide induces apoptosis and upregulation of TACE/ADAM17 and ADAM10 in an in vitro male germ cell line model
    (2011) Lizama, Carlos; Ludwig, Andreas; Moreno, Ricardo D.
    Etoposide is a widely used anticancer drug in the treatment of different tumors. Etoposide is known to activate a wide range of intracellular signals, which may in turn induce cellular responses other than apoptosis. ADAM10 and TACE/ADAM17 belong to a family of transmembrane extracellular metalloproteinases involved in paracrine/juxtacrine regulation of many signaling pathways. The aim of this work was to evaluate if etoposide induces upregulation of ADAM10 or TACE/ADAM17 in two cell lines (GC-1 and GC-2) derived from male germ cells. Results showed that etoposide induced apoptosis in a dose-response manner in both GC-1 and GC-2 cells. Apoptosis started to increase 6 h after etoposide addition in GC-2 cells, whereas the same was observed 18 h after addition to the GC-1 cells. Protein and mRNA levels of ADAM10 and TACE/ADAM17 increased 18.h after etoposide was removed from the GC-1 cells. In GC-2 cells, the protein levels of both proteins increased 12 h after etoposide was removed. ADAM] 0 mRNA increased after 3 h and then steadily decreased up to 12 h after removal, whereas TACE/ADAM17 mRNA decreased after etoposide removal. Finally, apoptosis was prevented in GC-1 and GC-2 cells by the addition of pharmacological inhibitors of ADAM10 and TACE/ADAM17 to the culture medium of etoposide-treated cells. Our results show for the first time that etoposide upregulates ADAM10 and TACE/ADAM17 mRNA and protein levels. In addition, we also show that ADAM] 0 and TACE/ADAM17 have a role in etoposide-induced apoptosis. (c) 2010 Elsevier B.V. All rights reserved.