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

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.
AuthorsZhe Liu, Chenyuan Liang, Zhuoyuan Zhang, Jian Pan, Hui Xia, Nanshan Zhong, Longjiang Li
JournalAnti-cancer drugs (Anticancer Drugs) Vol. 26 Issue 10 Pg. 1026-33 (Nov 2015) ISSN: 1473-5741 [Electronic] England
PMID26302210 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents
  • Sulfonamides
  • Toluene
  • Adenosine Triphosphate
  • 4-toluenesulfonamide
  • Adenosine Triphosphate (biosynthesis)
  • Antineoplastic Agents (pharmacology)
  • Apoptosis (drug effects)
  • Carcinoma, Squamous Cell (drug therapy)
  • Cell Line, Tumor (drug effects)
  • Humans
  • Lysosomes (drug effects, ultrastructure)
  • Mitochondria (drug effects, metabolism)
  • Necrosis
  • Sulfonamides (pharmacology)
  • Toluene (analogs & derivatives, pharmacology)
  • Tongue Neoplasms (drug therapy)

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