Activation of BK(Ca) channels in zoledronic acid-induced apoptosis of MDA-MB-231 breast cancer cells.
Activation of BK(Ca) channels in zoledronic acid-induced apoptosis of MDA-MB-231 breast cancer cells.
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唑来膦酸诱导 MDA-MB-231 乳腺癌细胞凋亡中 BKCa 通道的激活
DOI：
10.1371/journal.pone.0037451
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Xie MJ
中科院分区：
文献类型：
--
作者：
Ma YG;Liu WC;Dong S;Du C;Wang XJ;Li JS;Xie XP;Wu L;Ma DC;Yu ZB;Xie MJ
背景唑来膦酸是一种有效的含氮双膦酸盐，在体内外已被证明对乳腺癌具有直接的抗肿瘤和抗转移作用。特别是，肿瘤细胞凋亡已被认为在唑来膦酸治疗转移性乳腺癌中发挥重要作用。然而，确切的机制仍然不太清楚。在本研究中，我们研究了大电导钙激活钾（BKCa）通道在唑来膦酸诱导雌激素受体（ER）阴性的MDA-MB-231乳腺癌细胞凋亡中的具体作用。方法学/主要发现唑来膦酸对BKCa通道的作用通过全细胞和细胞贴附膜片钳技术进行研究。用免疫细胞化学、琼脂糖凝胶电泳DNA片段分析和流式细胞术检测细胞凋亡。MTT法和免疫细胞化学法检测细胞增殖情况。此外，这些发现在转染了功能性BKCa α-亚基（hSloα）的人胚肾293（HEK 293）细胞中得到了进一步证实。我们的结果清楚地表明，唑来膦酸直接增加BKCa通道的活性，然后唑来膦酸激活BKCa通道有助于诱导MDA-MB-231细胞凋亡。其机制可能与MDA-MB-231细胞内Ca ~（2+）水平升高及线粒体膜电位（Δ Km）去极化有关。结论BKCa通道激活是唑来膦酸诱导MDA-MB-231细胞凋亡的一条新的分子途径。
Background Zoledronic acid, one of the most potent nitrogen-containing biphosphonates, has been demonstrated to have direct anti-tumor and anti-metastatic properties in breast cancer in vitro and in vivo. In particular, tumor-cell apoptosis has been recognized to play an important role in the treatment of metastatic breast cancer with zoledronic acid. However, the precise mechanisms remain less clear. In the present study, we investigated the specific role of large conductance Ca2+-activated potassium (BKCa) channel in zoledronic acid-induced apoptosis of estrogen receptor (ER)-negative MDA-MB-231 breast cancer cells. Methodology/Principal Findings The action of zoledronic acid on BKCa channel was investigated by whole-cell and cell-attached patch clamp techniques. Cell apoptosis was assessed with immunocytochemistry, analysis of fragmented DNA by agarose gel electrophoresis, and flow cytometry assays. Cell proliferation was investigated by MTT test and immunocytochemistry. In addition, such findings were further confirmed with human embryonic kidney 293 (HEK293) cells which were transfected with functional BKCa α-subunit (hSloα). Our results clearly indicated that zoledronic acid directly increased the activities of BKCa channels, and then activation of BKCa channel by zoledronic acid contributed to induce apoptosis in MDA-MB-231 cells. The possible mechanisms were associated with the elevated level of intracellular Ca2+ and a concomitant depolarization of mitochondrial membrane potential (Δψm) in MDA-MB-231 cells. Conclusions Activation of BKCa channel was here shown to be a novel molecular pathway involved in zoledronic acid-induced apoptosis of MDA-MB-231 cells in vitro.
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影响因子：
3.8
作者：
Khaitan D;Sankpal UT;Weksler B;Meister EA;Romero IA;Couraud PO;Ningaraj NS
通讯作者：
Ningaraj NS
影响因子：
3.7
作者：
Abdullaev IF;Rudkouskaya A;Mongin AA;Kuo YH
通讯作者：
Kuo YH
DOI：
10.1186/bcr412
发表时间：
2002
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Senaratne SG;Colston KW
通讯作者：
Colston KW
影响因子：
2
作者：
Brevet, Marie;Ahidouch, Ahmed;Ouadid-Ahidouch, Halima
通讯作者：
Ouadid-Ahidouch, Halima
影响因子：
8.4
作者：
Neville-Webbe, H. L.;Coleman, R. E.
通讯作者：
Coleman, R. E.