Sulfasalazine, a potent suppressor of gastric cancer proliferation and metastasis by inhibition of xCT: Conventional drug in new use

Abstract

The aim of this study was to explore the role of sulfasalazine on proliferation and metastasis in gastric cancer by inhibition of xCT. The relationships between clinical characteristics and xCT expression were analysed. An immunohistochemical staining assay and Western blot were performed among gastric cancers and normal gastric tissues. qPCR and Western blot were also used to evaluate the mRNA and protein expression in the normal gastric cell and eight gastric cancer cells, respectively. CCK‐8 and colony formation assays were used to evaluate the effect of sulfasalazine on the proliferation and colony formation ability of three gastric cancers. The effect of sulfasalazine on the migration and invasion abilities of three cancer cells was assessed by the Transwell assay. xCT protein is up‐regulated in gastric cancer specimens and cells. Three gastric cancer cells with high, medium and low expression of xCT were selected for the following analyses. CCK‐8 assays revealed that sulfasalazine could attenuate the proliferation of HGC‐27 and AGS. Also, the colony formation assay revealed that sulfasalazine might attenuate the colony formation ability in HGC‐27 and AGS cells. Plus, the Transwell assays demonstrated that sulfasalazine might attenuate the migration and invasion abilities in HGC‐27 and AGS cells. In conclusion, higher expression of xCT is associated with advanced tumour stage and poor overall survival of gastric cancer. Sulfasalazine can attenuate the proliferation, colony formation, metastasis and invasion of gastric cancer in vitro. Further study is required to validate our findings.

Neutrophil-Derived IL-6 Potentially Drives Ferroptosis Resistance in B Cells in Lupus Kidney

“…Considering B cells in the lupus kidney exhibited higher expression of SLC7A11 (Supplementary figures 5A and 5B ), a downstreaming molecule mediated by the IL-6 in mediating ferroptosis resistance [ 16 ]. We treated the cocultured B cells and neutrophils with sulfasalazine (an inhibitor of SLC7A11 [ 21 , 23 ]). After sulfasalazine, the expression level of SLC7A11 was significantly downregulated (Supplementary figure 6 ), the Fe 2+ signal (Figures 3(h) and 3(i) ) and lipid peroxidation (Figures 3(j) and 3(k) ) was significantly increased in B cells isolated from lupus mouse, meanwhile the intracellular GSSH and GSH were also altered accordingly (Figures 3(l) and 3(m) ), indicating IL-6 facilitates ferroptosis resistance in lupus B cells via SLC7A11.…”

The Role of Cystine/Glutamate Antiporter SLC7A11/xCT in the Pathophysiology of Cancer

“…Tanshione IIA, an active compound isolated from the rhizome of Chinese herb Danshen has been shown to block gastric cancer stem cells via ferroptosis induction and SLC7A11 downregulation ( 119 ). SLC7A11 inhibition via sulfasalazine reduced colony formation, proliferation, metastasis, and invasion of gastric cancer cells in vitro ( 120 ).…”

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“…SLC7A11 immunotargeted therapies-such as the SLC7A11-targeted DNA vaccination [108], a virus-like particle immunotherapy targeting the SLC7A11 protein [109], and an anti-SLC7A11 viral vaccine based on the bovine herpesvirus 4 vector [110]-also impede the progression of breast cancer by inhibiting SLC7A11. [103], GC [111], PC [112], GBM [113], LUAD [114]…”