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.
Highlights
Oral squamous cell carcinoma (OSCC) is the most common malignancy of oral cavity, and the sixth most frequently diagnosed cancer worldwide (Jemal et al, 2011; Siegel et al, 2012)
SSZ induced autophagic cell death, increased microtubule-associated protein 1 light chain (MAP1LC; known as LC) 3-II levels, as well as induced punctate acidic vesicular organelle (AVO) and MDC staining, resulted in autophagic cell death. 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
We investigated the possibility that in HSC-4 cells after treatment with the vehicle or 0.5, SSZ has chemotherapeutic potential for the treatment of
Summary
Oral squamous cell carcinoma (OSCC) is the most common malignancy of oral cavity, and the sixth most frequently diagnosed cancer worldwide (Jemal et al, 2011; Siegel et al, 2012). Most OSCC patients are usually diagnosed after the cancer has reached an advanced stage, and this tumor type is associated with poor prognosis. Some chemotherapeutic agents such as taxol, 5-FU, and cisplatin, which have been used to treat OSCC, have associated with side effects, which include immunosuppression, nausea/vomiting, oral ulcers, and hair loss. Sulfasalazine (SSZ) is composed of sulfapyridine and mesalazine (mesalamine, 5-aminosalicylic acid). It is an anti-inflammatory drug that has been used routinely for decades to treat inflammatory bowel disease and rheumatoid arthritis (Ogrendik, 2013). The therapeutic effects of SSZ are primarily attributed to mesalazine, which has favorable side-effect profile (Ogrendik, 2013)
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