Gastric cancer is a commonly diagnosed form of cancer, and cisplatin is commonly used as a chemotherapy drug for treating it. However, the side effects of cisplatin may reduce patients?… Click to show full abstract
Gastric cancer is a commonly diagnosed form of cancer, and cisplatin is commonly used as a chemotherapy drug for treating it. However, the side effects of cisplatin may reduce patients? willingness to use it. Seselin, a derivative of coumarin, has been found to have anticancer properties as well as anticoagulant effects. In this study, we investigated the effect of seselin on promoting cisplatininduced gastric cancer cell death using the cell proliferation reagent WST-1, BrdU incorporation and lactate dehydrogenase release. The role of seselin and cisplatin in the apoptosis of gastric cancer cells was analyzed using a phospho-kinase array and Western blot analysis. Seselin did not affect G2/M stasis, but it promoted cell death in AGS cells treated with cisplatin. Phospho-kinase array analysis revealed that cisplatin regulates intracellular p53 phosphorylation, while seselin regulates intracellular ?-catenin expression by affecting the phosphorylation of glycogen synthase kinase-3 beta (GSK-3?), extracellular-signal-regulated kinase (ERK) and Src tyrosine kinase. Seselin and cisplatin promote the apoptosis of gastric cancer cells by the synergistic effect of two distinct signaling pathways. These findings suggest that seselin may be used as a complementary therapy to reduce the clinical dose of chemotherapy.
               
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