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Para-toluenesulfonamide induces tongue squamous cell carcinoma cell death through disturbing lysosomal stability.

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机构: [1]Department of Head and Neck Oncology , West China Hospital of Stomatology, Sichuan University, Chengdu [2]State Key Laboratory of Oral Diseases , West China Hospital of Stomatology, Sichuan University, Chengdu [3]Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu [4]State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Diseases, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
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关键词: apoptosis lysosome mitochondria para-toluenesulfonamide tongue squamous cell carcinoma

摘要:
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.

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出版当年[2015]版:
大类 | 4 区 医学
小类 | 4 区 肿瘤学 4 区 药学
最新[2023]版:
大类 | 4 区 医学
小类 | 4 区 肿瘤学 4 区 药学
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第一作者机构: [1]Department of Head and Neck Oncology , West China Hospital of Stomatology, Sichuan University, Chengdu [2]State Key Laboratory of Oral Diseases , West China Hospital of Stomatology, Sichuan University, Chengdu
通讯作者:
通讯机构: [1]Department of Head and Neck Oncology , West China Hospital of Stomatology, Sichuan University, Chengdu [2]State Key Laboratory of Oral Diseases , West China Hospital of Stomatology, Sichuan University, Chengdu [*1]Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, 14#, 3rd Section of Renmin South Road, Chengdu 610041, China
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