Identification of an antitumor effect of demethylzeylasteral on human gastric cancer cells

Gastric cancer is a common malignancy in China, with the second highest mortality rate worldwide. Advanced gastric cancer usually exhibits a poor prognosis with a low 5-year survival rate. Therefore, developing novel drugs for the treatment of this cancer will be beneficial for patients. Demethylzeylasteral, an extract of tripterygium wilfordii, has shown positive anticancer activities. However, the possible antitumor effect of demethylzeylasteral on gastric cancer cells and its underlying molecular mechanism remain to be determined. In the present study, the Cell Counting Kit-8 and colony formation assays revealed that demethylzeylasteral impeded the proliferation of human gastric cancer cells in a dose-dependent manner. Furthermore, the Transwell assay identified an inhibitory effect of demethylzeylasteral on the migration of MKN-45 cells, while flow cytometry found that treatment with demethylzeylasteral induced apoptosis and decreased the mitochondrial membrane potential in the cancer cells. Further investigation revealed that demethylzeylasteral downregulated the phosphorylation of ERK1/2, AKT, and GSK-3β in MKN-45 cells. Notably, decreased expression of Bcl-2 and increased expression of Bax, cleaved caspase-3, cleaved caspase-9 and cleaved PARP were detected in the cancer cells treated with demethylzeylasteral. The present study demonstrated that demethylzeylasteral exhibits therapeutic potential for gastric cancer.

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