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

Liu Z, Liang C, Zhang Z, Pan J, Xia H, Zhong N, Li L - Anticancer Drugs (2015)

Bottom Line: Para-toluenesulfonamide (PTS) has been implicated with anticancer effects against a variety of tumors.Next, the effects of PTS on cell viability, invasion, and cell death were determined.Lysosomal integrity assay and western blot showed that PTS increased lysosomal membrane permeabilization associated with activation of lysosomal cathepsin B.

View Article: PubMed Central - PubMed

Affiliation: aDepartment 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.

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Para-toluenesulfonamide (PTS) induces the release of mitochondrial cytochrome c and inhibits ATP biosynthesis. (a) Western blot analysis of Tca-8113 cells after 40 μmol/l PTS treatment for 1 h. Cytosolic cytochrome c released from mitochondria is shown. β-Actin was used as a loading control. (b) Tca-8113 cells were treated with 40 μmol/l PTS or dimethyl sulfoxide for 24–48 h. The effects of PTS on ATP biosynthesis were assessed by measuring chemiluminescence. Data represent the mean±SD of three independent experiments. *P<0.05.
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Figure 4: Para-toluenesulfonamide (PTS) induces the release of mitochondrial cytochrome c and inhibits ATP biosynthesis. (a) Western blot analysis of Tca-8113 cells after 40 μmol/l PTS treatment for 1 h. Cytosolic cytochrome c released from mitochondria is shown. β-Actin was used as a loading control. (b) Tca-8113 cells were treated with 40 μmol/l PTS or dimethyl sulfoxide for 24–48 h. The effects of PTS on ATP biosynthesis were assessed by measuring chemiluminescence. Data represent the mean±SD of three independent experiments. *P<0.05.

Mentions: Increased lysosomal permeability is reported to induce mitochondrial damage and the release of proapoptotic factors 6. We therefore investigated the cytosolic cytochrome c released from the mitochondria after PTS treatment. Western blot showed that 40 μmol/l PTS treatment significantly induced cytosolic cytochrome c expression in Tca-8113 cells (Fig. 4a). As the mitochondria are at the core of cellular energy metabolism and also the major organelles for ATP generation, we then asked whether PTS regulates mitochondrial ATP biosynthesis. As shown in Fig. 4b, PTS treatment significantly inhibited mitochondrial ATP biosynthesis in a dose-dependent manner. 40 μmol/l PTS treatment for 1 h attenuated ATP biosynthesis to 65.8%. These results suggest that PTS induces mitochondrial damage and exerts a metabolic arrest effect on cancer cells.


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

Liu Z, Liang C, Zhang Z, Pan J, Xia H, Zhong N, Li L - Anticancer Drugs (2015)

Para-toluenesulfonamide (PTS) induces the release of mitochondrial cytochrome c and inhibits ATP biosynthesis. (a) Western blot analysis of Tca-8113 cells after 40 μmol/l PTS treatment for 1 h. Cytosolic cytochrome c released from mitochondria is shown. β-Actin was used as a loading control. (b) Tca-8113 cells were treated with 40 μmol/l PTS or dimethyl sulfoxide for 24–48 h. The effects of PTS on ATP biosynthesis were assessed by measuring chemiluminescence. Data represent the mean±SD of three independent experiments. *P<0.05.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4588602&req=5

Figure 4: Para-toluenesulfonamide (PTS) induces the release of mitochondrial cytochrome c and inhibits ATP biosynthesis. (a) Western blot analysis of Tca-8113 cells after 40 μmol/l PTS treatment for 1 h. Cytosolic cytochrome c released from mitochondria is shown. β-Actin was used as a loading control. (b) Tca-8113 cells were treated with 40 μmol/l PTS or dimethyl sulfoxide for 24–48 h. The effects of PTS on ATP biosynthesis were assessed by measuring chemiluminescence. Data represent the mean±SD of three independent experiments. *P<0.05.
Mentions: Increased lysosomal permeability is reported to induce mitochondrial damage and the release of proapoptotic factors 6. We therefore investigated the cytosolic cytochrome c released from the mitochondria after PTS treatment. Western blot showed that 40 μmol/l PTS treatment significantly induced cytosolic cytochrome c expression in Tca-8113 cells (Fig. 4a). As the mitochondria are at the core of cellular energy metabolism and also the major organelles for ATP generation, we then asked whether PTS regulates mitochondrial ATP biosynthesis. As shown in Fig. 4b, PTS treatment significantly inhibited mitochondrial ATP biosynthesis in a dose-dependent manner. 40 μmol/l PTS treatment for 1 h attenuated ATP biosynthesis to 65.8%. These results suggest that PTS induces mitochondrial damage and exerts a metabolic arrest effect on cancer cells.

Bottom Line: Para-toluenesulfonamide (PTS) has been implicated with anticancer effects against a variety of tumors.Next, the effects of PTS on cell viability, invasion, and cell death were determined.Lysosomal integrity assay and western blot showed that PTS increased lysosomal membrane permeabilization associated with activation of lysosomal cathepsin B.

View Article: PubMed Central - PubMed

Affiliation: aDepartment 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.

Show MeSH
Related in: MedlinePlus