title: Sulfasalazine induces autophagic cell death in oral cancer cells via Akt and ERK pathways.
abstract: Sulfasalazine (SSZ) is an anti-inflammatory drug that has been used to treat inflammatory bowel disease and rheumatoid arthritis for decades. Recently, some reports have suggested that SSZ also has anti-cancer properties against human tumors. However, little is known about the effects of SSZ on oral cancer. The aim of this study was to investigate the anti-cancer effects of SSZ in oral squamous cell carcinoma (OSCC) cells and to elucidate the mechanisms involved. The authors investigated the anti-proliferative effect of SSZ using the MTT method in HSC-4 cells (an OSCC cell line). Cell cycle analysis, acidic vesicular organelle (AVO) staining, monodansylcadaverine (MDC) staining and Western blotting were also conducted to investigate the cytotoxic mechanism of SSZ. SSZ significantly inhibited the proliferation of HSC-4 cells in a dose-dependent manner. In addition, SSZ induced autophagic cell death, increased microtubule-associated protein 1 light chain (MAP1- LC; also known as LC) 3-II levels, as well as induced punctate AVO and MDC staining, resulted in autophagic cell death. Furthermore, these observations were accompanied by the inhibition of the Akt pathway and the activation of ERK pathway. These results suggest that SSZ promotes autophagic cell death via Akt and ERK pathways and has chemotherapeutic potential for the treatment of oral cancer.
authors.affiliation: Department of Oral Pathology, School of Dentistry, Institute of Translational Dental Sciences, Pusan National University, South Korea E-mail : apollon@pusan.ac.kr.
authors.forename: Hye-Yeon
authors.initials: HY
authors.lastname: Han
authors.forename: Hyungwoo
authors.initials: H
authors.lastname: Kim
authors.forename: Sung-Hee
authors.initials: SH
authors.lastname: Jeong
authors.forename: Do-Seon
authors.initials: DS
authors.lastname: Lim
authors.forename: Mi Heon
authors.initials: MH
authors.lastname: Ryu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009062:Mouth Neoplasms / Q000188:drug therapy*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors*; D012460:Sulfasalazine / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D008869:Microtubule-Associated Proteins; D012460:Sulfasalazine; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases