JS-K, a nitric oxide-releasing prodrug, induces breast cancer cell death while sparing normal mammary epithelial cells.
JS-K, a nitric oxide-releasing prodrug, induces breast cancer cell death while sparing normal mammary epithelial cells.
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DOI：
10.3892/ijo.2011.925
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发表时间：
2011-04
影响因子：
5.2
通讯作者：
Tari AM
中科院分区：
文献类型：
--
作者：
McMurtry V;Saavedra JE;Nieves-Alicea R;Simeone AM;Keefer LK;Tari AM
减少副作用的靶向治疗是癌症研究的主要目标。我们研究了JS-K（一种一氧化氮（NO）前药，设计用于在适当激活时释放高水平NO）对人乳腺癌细胞系、非转化人MCF-10A乳腺细胞和正常人乳腺上皮细胞（HMEC）的影响。采用细胞活力测定、流式细胞术、电镜和Western blot分析等方法研究JS-K对乳腺癌细胞和乳腺上皮细胞的作用。孵育3天后，JS-K对乳腺癌细胞的IC 50范围为0.8至3 μ M。然而，在10 μ M浓度下，JS-K仅使MCF-10A细胞的活力降低20%，并且HMEC不受10 μ M JS-K的影响。流式细胞仪检测结果显示，JS-K可增加乳腺癌细胞凋亡率。有趣的是，流式细胞术表明JS-K增加了乳腺癌细胞中酸性囊泡细胞器的形成，表明JS-K诱导了乳腺癌细胞中的自噬。电子显微镜证实，JS-K处理的乳腺癌细胞发生自噬细胞死亡。Western blot分析显示，JS-K诱导乳腺癌细胞中另一种自噬标志物微管轻链3-II的表达。然而，JS-K在正常人乳腺上皮细胞中不诱导凋亡或自噬。这些数据表明，JS-K选择性地诱导乳腺癌细胞中的程序性细胞死亡，而在相同条件下保留正常乳腺上皮细胞。JS-K的选择性抗肿瘤活性保证了其在乳腺肿瘤中的进一步研究。
Targeted therapy with reduced side effects is a major goal in cancer research. We investigated the effects of JS-K, a nitric oxide (NO) prodrug designed to release high levels of NO when suitably activated, on human breast cancer cell lines, on non-transformed human MCF-10A mammary cells, and on normal human mammary epithelial cells (HMECs). Cell viability assay, flow cytometry, electron microscopy, and Western blot analysis were used to study the effects of JS-K on breast cancer and on mammary epithelial cells. After a 3-day incubation, the IC50s of JS-K against the breast cancer cells ranged from 0.8 to 3 μM. However, JS-K decreased the viability of the MCF-10A cells by only 20% at 10-μM concentration, and HMECs were unaffected by 10 μM JS-K. Flow cytometry indicated that JS-K increased the percentages of breast cancer cells under-going apoptosis. Interestingly, flow cytometry indicated that JS-K increased acidic vesicle organelle formation in breast cancer cells, suggesting that JS-K induced autophagy in breast cancer cells. Electron microscopy confirmed that JS-K-treated breast cancer cells underwent autophagic cell death. Western blot analysis showed that JS-K induced the expression of microtubule light chain 3-II, another autophagy marker, in breast cancer cells. However, JS-K did not induce apoptosis or autophagy in normal human mammary epithelial cells. These data indicate that JS-K selectively induces programmed cell death in breast cancer cells while sparing normal mammary epithelial cells under the same conditions. The selective anti-tumor activity of JS-K warrants its further investigation in breast tumors.
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影响因子：
4.7
作者：
Heigold, S;Sers, C;Bauer, G
通讯作者：
Bauer, G
DOI：
10.1083/jcb.152.4.657
发表时间：
2001-02-19
期刊：
The Journal of cell biology
影响因子：
--
作者：
Mizushima N;Yamamoto A;Hatano M;Kobayashi Y;Kabeya Y;Suzuki K;Tokuhisa T;Ohsumi Y;Yoshimori T
通讯作者：
Yoshimori T
影响因子：
8.8
作者：
Howie, A F;Miller, W R;Hawkins, R A;Hutchinson, A R;Beckett, G J
通讯作者：
Beckett, G J
影响因子：
4.8
作者：
Petiot, A;Ogier-Denis, E;Codogno, P
通讯作者：
Codogno, P
DOI：
10.1016/j.bbrc.2004.10.010
发表时间：
2004-12-03
影响因子：
3.1
作者：
Bishop, A;Yet, SF;Demple, B
通讯作者：
Demple, B