Division of Bioinformation, Department of Physiology, Hyogo College of Medicine, Mukogawa-cho, Nishinomiya, Japan.
Cancer Lett. 2012 Aug 1;321(1):65-72. doi: 10.1016/j.canlet.2012.02.023. Epub 2012 Feb 28.
Extracellular adenosine induced apoptosis of MCF-7 human breast cancer cells in a concentration (10μM-10mM)- and treatment time (24-72h)-dependent manner, and the effect was inhibited by the adenosine transporter inhibitor dipyridamole, but not an inhibitor of adenosine kinase, an inhibitor of AMP-activated protein kinase, or inhibitors for A(1), A(2a), A(2b), and A(3) adenosine receptors. No significant activation of caspase-7, -8, or -9 was obtained with adenosine. Adenosine promoted translocation of apoptosis-inducing factor (AIF)-homologous mitochondrion-associated inducer of death (AMID) from the cytosol into the nucleus, although the total amount of AMID was not affected. Adenosine-induced MCF-7 cell death was abrogated by knocking-down AMID. The results of the present study indicate that intracellularly transported adenosine induces MCF-7 cell apoptosis by accumulating AMID in the nucleus in a caspase-independent manner.
细胞外腺苷以浓度（10μM-10mM）和作用时间（24-72 小时）依赖的方式诱导 MCF-7 人乳腺癌细胞凋亡，该效应可被腺苷转运蛋白抑制剂双嘧达莫抑制，但不被腺苷激酶抑制剂、AMP 激活的蛋白激酶抑制剂、A(1)、A(2a)、A(2b)和 A(3) 腺苷受体抑制剂抑制。用腺苷未获得 caspase-7、-8 或 -9 的明显激活。腺苷促进凋亡诱导因子（AIF）同源线粒体相关死亡诱导因子（AMID）从细胞质向核内易位，尽管 AMID 的总量不受影响。用 AMID 敲低可阻断腺苷诱导的 MCF-7 细胞死亡。本研究结果表明，细胞内转运的腺苷通过以不依赖于半胱天冬酶的方式使 AMID 在核内积累诱导 MCF-7 细胞凋亡。
