Chloroquine is a zinc ionophore.
Chloroquine is a zinc ionophore.
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DOI：
10.1371/journal.pone.0109180
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Ding WQ
中科院分区：
文献类型：
--
作者：
Xue J;Moyer A;Peng B;Wu J;Hannafon BN;Ding WQ
氯喹是一种已确定的抗疟药，最近在临床试验中对其抗癌活性进行了测试。氯喹的有利作用似乎是由于其能够使癌细胞对化疗、放疗敏感并诱导细胞凋亡。本研究探讨了锌离子与氯喹在人卵巢癌细胞系（A2780）中的相互作用。氯喹以浓度依赖的方式增强A2780细胞对锌的摄取，用荧光锌探针检测。这种增强被TPEN（一种高亲和力金属结合化合物）减弱，表明锌摄取的特异性。此外，添加铜或铁离子对氯喹诱导的锌吸收没有影响。细胞内锌分布的荧光显微镜检查表明，游离锌离子在加入氯喹后更集中在溶酶体中，这与先前的报告显示氯喹抑制溶酶体功能一致。氯喹与锌联合应用可增强氯喹对A2780细胞的毒性并诱导其凋亡。因此，氯喹是一种锌离子载体，这一特性可能有助于氯喹的抗癌活性。
Chloroquine is an established antimalarial agent that has been recently tested in clinical trials for its anticancer activity. The favorable effect of chloroquine appears to be due to its ability to sensitize cancerous cells to chemotherapy, radiation therapy, and induce apoptosis. The present study investigated the interaction of zinc ions with chloroquine in a human ovarian cancer cell line (A2780). Chloroquine enhanced zinc uptake by A2780 cells in a concentration-dependent manner, as assayed using a fluorescent zinc probe. This enhancement was attenuated by TPEN, a high affinity metal-binding compound, indicating the specificity of the zinc uptake. Furthermore, addition of copper or iron ions had no effect on chloroquine-induced zinc uptake. Fluorescent microscopic examination of intracellular zinc distribution demonstrated that free zinc ions are more concentrated in the lysosomes after addition of chloroquine, which is consistent with previous reports showing that chloroquine inhibits lysosome function. The combination of chloroquine with zinc enhanced chloroquine's cytotoxicity and induced apoptosis in A2780 cells. Thus chloroquine is a zinc ionophore, a property that may contribute to chloroquine's anticancer activity.
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影响因子：
4.7
作者：
Aiba I;West AK;Sheline CT;Shuttleworth CW
通讯作者：
Shuttleworth CW
影响因子：
5.7
作者：
Ding, Wei-Qun;Liu, Bolin;Lind, Stuart E.
通讯作者：
Lind, Stuart E.
DOI：
10.1097/jto.0b013e318262de4a
发表时间：
2012-10
期刊：
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
影响因子：
--
作者：
Goldberg SB;Supko JG;Neal JW;Muzikansky A;Digumarthy S;Fidias P;Temel JS;Heist RS;Shaw AT;McCarthy PO;Lynch TJ;Sharma S;Settleman JE;Sequist LV
通讯作者：
Sequist LV
影响因子：
120.7
作者：
Solomon, Daniel H.;Massarotti, Elena;Schneeweiss, Sebastian
通讯作者：
Schneeweiss, Sebastian
影响因子：
11.2
作者：
Ding, WQ;Liu, BL;Lind, SE
通讯作者：
Lind, SE