1. Tamoxifen induces oxidative stress and apoptosis in oestrogen receptor-negative human cancer cell lines
- Author
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C Gaggini, Giovanni Scambia, Gabriella Ferrandina, P. Benedetti Panici, Andrea Fattorossi, Mariagrazia Distefano, Cristiano Ferlini, Salvatore Mancuso, Maria Marone, and G Isola
- Subjects
Cancer Research ,medicine.medical_specialty ,Antineoplastic Agents, Hormonal ,Cell ,Biology ,medicine.disease_cause ,Jurkat cells ,NF-κB ,Jurkat Cells ,stomatognathic system ,Internal medicine ,Tumor Cells, Cultured ,medicine ,Humans ,Phosphorylation ,skin and connective tissue diseases ,tamoxifen ,Cell growth ,NF-kappa B ,apoptosis ,Regular Article ,Antiestrogen ,Oxidative Stress ,Endocrinology ,medicine.anatomical_structure ,Proto-Oncogene Proteins c-bcl-2 ,Receptors, Estrogen ,Oncology ,Apoptosis ,Cancer cell ,Cancer research ,Oxidation-Reduction ,Cell Division ,hormones, hormone substitutes, and hormone antagonists ,Tamoxifen ,Oxidative stress ,medicine.drug - Abstract
Recent data have demonstrated that the anti-oestrogen tamoxifen (TAM) is able to facilitate apoptosis in cancer cells not expressing oestrogen receptor (ER). In an attempt to identify the biochemical pathway for this phenomenon, we investigated the role of TAM as an oxidative stress agent. In two ER-negative human cancer cell lines, namely T-leukaemic Jurkat and ovarian A2780 cancer cells, we have demonstrated that TAM is able to generate oxidative stress, thereby causing thiol depletion and activation of the transcriptional factor NF-κB. As described for other oxidative agents, TAM was able to induce either cell proliferation or apoptosis depending on the dose. When used at the lowest dose tested (0.1 μM), a slight proliferative effect of TAM was noticed in terms of cell counts and DNA synthesis rate, whereas at higher doses (10 μM) a consistent occurrence of apoptosis was detected. Importantly, the induction of apoptosis by TAM is not linked to down-regulation or functional inactivation by phosphorylation of the antiapoptotic bcl-2 protein. © 1999 Cancer Research Campaign
- Published
- 1998
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