Para-toluenesulfonamide induces tongue squamous cell carcinoma cell death through disturbing lysosomal stability.
Para-toluenesulfonamide induces tongue squamous cell carcinoma cell death through disturbing lysosomal stability.
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对甲苯磺酰胺通过干扰溶酶体稳定性诱导舌鳞状细胞癌细胞死亡
DOI：
10.1097/cad.0000000000000283
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发表时间：
2015-11
影响因子：
2.3
通讯作者：
Li L
中科院分区：
文献类型：
--
作者：
Liu Z;Liang C;Zhang Z;Pan J;Xia H;Zhong N;Li L
对甲苯磺酰胺（PTS）与多种肿瘤的抗癌作用有关。本研究以体外培养的人舌鳞癌细胞株Tca-8113为模型，观察了PTS对Tca-8113细胞的抑制作用，并探讨了PTS对Tca-8113细胞溶酶体和线粒体的影响。高效液相色谱显示PTS选择性地在Tca-8113细胞中蓄积，而在正常成纤维细胞中浓度相对较低。接下来，测定PTS对细胞活力、侵袭和细胞死亡的影响。PTS能显著抑制Tca-8113细胞的生长和侵袭能力，并增加癌细胞的死亡率。流式细胞仪分析和乳酸脱氢酶释放试验表明，PTS诱导癌细胞死亡，同时激活凋亡和坏死。形态学观察发现，PTS可引起细胞皱缩、核固缩、凋亡小体和次级溶酶体形成，提示PTS可能通过破坏溶酶体的稳定性而导致细胞死亡。溶酶体完整性分析和蛋白质印迹显示，PTS增加溶酶体膜透性与溶酶体组织蛋白酶B的激活。最后，PTS显示抑制ATP生物合成并诱导线粒体细胞色素c的释放。因此，我们的研究结果为PTS在癌症治疗中的应用提供了新的见解。
Para-toluenesulfonamide (PTS) has been implicated with anticancer effects against a variety of tumors. In the present study, we investigated the inhibitory effects of PTS on tongue squamous cell carcinoma (Tca-8113) and explored the lysosomal and mitochondrial changes after PTS treatment in vitro. High-performance liquid chromatography showed that PTS selectively accumulated in Tca-8113 cells with a relatively low concentration in normal fibroblasts. Next, the effects of PTS on cell viability, invasion, and cell death were determined. PTS significantly inhibited Tca-8113 cells’ viability and invasive ability with increased cancer cell death. Flow cytometric analysis and the lactate dehydrogenase release assay showed that PTS induced cancer cell death by activating apoptosis and necrosis simultaneously. Morphological changes, such as cellular shrinkage, nuclear condensation as well as formation of apoptotic body and secondary lysosomes, were observed, indicating that PTS might induce cell death through disturbing lysosomal stability. Lysosomal integrity assay and western blot showed that PTS increased lysosomal membrane permeabilization associated with activation of lysosomal cathepsin B. Finally, PTS was shown to inhibit ATP biosynthesis and induce the release of mitochondrial cytochrome c. Therefore, our findings provide a novel insight into the use of PTS in cancer therapy.