Influence of the xc-cystine/glutamate antiporter inhibitor sulfasalazine on the growth of head and neck squamous cell carcinoma cell lines

Introduction:

Sulfasalazine (SSZ) inhibits the xc- cystine/glutamate antiporter. This transporter is required for the maintenance of high intracellular glutathione levels thereby promoting chemotherapy-resistance of head and neck squamous cell carcinoma (HNSCC) cells as previously reported by our group and others. The aim of the present study was to evaluate the sensitivity of HNSCC cells to SSZ. Methods. HNSCC (UM-SCC-1, -3, -4, -6, -14A, -22B, -27, UT-SCC-24A, -26A) cell lines and HaCaT cells were cultured under standard conditions. Cells were incubated at 0 – 2000µM SSZ and subjected to FACS, Western blot (WB) analysis and immunocytochemistry. Antibodies directed against MAP-LC3β, p21CIP1/WAF1, p27KIP1 and β-tubulin were used in WB analysis and immunocytochemistry. Results. At 2000µM SSZ and without additional application of a chemotherapeutic agent, all 10 cell lines responded to a different extent with cell death, whereas no detectable response was seen at ≤200µM SSZ. Representative, differentially responsive HNSCC cell lines (UM-SCC-1, -3, UT-SCC-26A) and HaCaT cells were further investigated at 0, 200, 650, 1100, 1550, 2000µM SSZ. All tested cells exhibited a differential dose-dependent response to SSZ treatment showing induction of p21CIP1/WAF1 and MAP-LC3β as well as cells in the subG1 phase (= dead cells) of the cell cycle and a paradox reduction of p27KIP1 expression levels. Conclusions. SSZ treatment alone, without simultaneous addition of chemotherapeutic agents, inhibits HNSCC cell growth in vitro. This could be explained by the, in tumor cells prevailing, cytotoxic stress that could be compensated by glutathione.

Publication History

Publication Date:
18 April 2018 (online)