Para-toluenesulfonamide induces tongue squamous cell carcinoma cell death through disturbing lysosomal stability
Zhe Liu1, Chenyuan Liang, Zhuoyuan Zhang
1aDepartment of Head and Neck Oncology bState Key Laboratory of Oral Diseases cDepartment of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu dState Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Diseases, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
Abstract:
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.
Insights
Para-toluenesulfonamide (PTS) effectively inhibits tongue squamous cell carcinoma (Tca-8113) by inducing cell death through lysosomal and mitochondrial damage. This study reveals PTS
Area of Science:
- Oncology
- Cell Biology
- Pharmacology
Background:
- Para-toluenesulfonamide (PTS) exhibits potential anticancer properties against various tumors.
- Investigating PTS' specific effects on tongue squamous cell carcinoma (Tca-8113) is crucial for targeted therapy development.
Purpose of the Study:
- To evaluate the inhibitory effects of PTS on Tca-8113 cells.
- To elucidate the mechanisms of PTS-induced cell death, focusing on lysosomal and mitochondrial pathways.
- To assess PTS selectivity for cancer cells over normal fibroblasts.
Main Methods:
- High-performance liquid chromatography (HPLC) for PTS accumulation analysis.
- Cell viability, invasion, and cell death assays (flow cytometry, lactate dehydrogenase release).
- Morphological analysis, lysosomal integrity assays, and Western blotting for cathepsin B and cytochrome c.
- ATP biosynthesis and mitochondrial function assessment.
Main Results:
- PTS selectively accumulated in Tca-8113 cells.
- PTS significantly reduced cell viability and invasion while increasing cell death.
- PTS induced simultaneous apoptosis and necrosis, disrupting lysosomal stability and activating cathepsin B.
- PTS inhibited ATP production and triggered mitochondrial cytochrome c release.
Conclusions:
- PTS demonstrates potent inhibitory effects on tongue squamous cell carcinoma.
- PTS induces cancer cell death via lysosomal and mitochondrial pathways.
- PTS shows potential as a therapeutic agent for tongue cancer.
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