Para-toluenesulfonamide induces tongue squamous cellcarcinoma cell death through disturbing lysosoma

Para-toluenesulfonamide (PTS) has been implicated withanticancer effects against a variety of tumors. In the presentstudy, we investigated the inhibitory effects of PTS ontongue squamous cell carcinoma (Tca-8113) and exploreothe lysosomal and mitochondrial changes after PTStreatment in vitro. High-performance liquid chromatographyshowed that PTS selectively accumulated in Tca-8113 cellswith a relatively low concentration in normal fibroblasts.Next, the effects of PTS on cell viability, invasion, and celldeath were determined. PTS significantly inhibited Tca-8113cells' viability and invasive ability with increased cancer celdeath. Flow cytometric analysis and the lactatedehydrogenase release assay showed that PTS inducedcancer cell death by activating apoptosis and necrosissimultaneously. Morphological changes, such as cellularshrinkage, nuclear condensation as well as formation ofapoptotic body and secondary lysosomes, were observedindicating that PTS might induce cell death throughdisturbing lysosomal stability. Lysosomal integrity assayand western blot showed that PTS increased lysosomal

membrane permeabilization associated with activation oflysosomal cathepsin B. Finally, PTS was shown to inhibitATP biosynthesis and induce the release of mitochondriacvtochrome c.Therefore our findings provide a novel insighinto the use of PTS in cancer therapy. Anti-Cancer Drugs26:1026-1033 Copyright C 2015 Wolters Kluwer Health, IncAll rights reserved.

Anti-Cancer Drugs 2015,26:1026-1033

Keywords: apoptosis, lysosome, mitochondria, para-toluenesulfonamide.tongue squamous cell carcinoma

Department of Head and Neck Oncology,State Key Laboratory of OralDiseases,“Department of Oral and Maxillofacial Surgery, West China Hospital ofStomatology, Sichuan University, Chengdu and “State Key Laboratory ofRespiratory Disease, Guangzhou lnstitute of Respiratory Diseases, First AffiliatedHospital, Guangzhou Medical University, Guangzhou, China

Correspondence to Longjiang Li DDS, PhD, Department of Head and NeckOncology, West China Hospital of Stomatology, Sichuan University, 14#, 3rdSection of Renmin South Road, Chengdu 610041, ChinaTel/fax: +86 28 85501428: e-mail: muzili63@163.com

Received 15 April 2015 Revised form accepted 23 July 2015