Tamoxifen induces oxidative stress and apoptosis in oestrogen receptor-negative human cancer cell lines.
Tamoxifen induces oxidative stress and apoptosis in oestrogen receptor-negative human cancer cell lines.
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DOI：
10.1038/sj.bjc.6690042
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发表时间：
1999-01
影响因子：
8.8
通讯作者：
Mancuso, S
中科院分区：
文献类型：
--
作者：
Ferlini, C;Scambia, G;Marone, M;Distefano, M;Gaggini, C;Ferrandina, G;Fattorossi, A;Isola, G;Benedetti Panici, P;Mancuso, S
最近的数据表明，抗雌激素他莫昔芬（TAM）能够促进不表达雌激素受体（ER）的癌细胞的凋亡。在试图确定这种现象的生化途径，我们研究了TAM作为氧化应激剂的作用。在两个ER阴性的人类癌细胞系，即T-白血病Jurkat和卵巢A2780癌细胞中，我们已经证明了TAM能够产生氧化应激，从而导致巯基耗尽和转录因子NF-κB的激活。如对其他氧化剂所述，TAM能够根据剂量诱导细胞增殖或凋亡。当以最低试验剂量（0.1 μM）使用时，在细胞计数和DNA合成率方面观察到TAM的轻微增殖效应，而在较高剂量（10 μM）下检测到细胞凋亡的一致发生。重要的是，TAM诱导细胞凋亡与抗凋亡bcl-2蛋白磷酸化引起的下调或功能失活无关。© 1999癌症研究运动
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