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Identification of an antitumor effect of demethylzeylasteral on human gastric cancer cells
Yang Yang1, Menglin Zhao1, Ting Hu1
1Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical College, Anhui Province Key Laboratory of Translational Cancer Research, Bengbu Medical College, Bengbu, Anhui 233004, P.R. China.
Abstract:
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.
Insights
Demethylzeylasteral, a natural compound, effectively inhibits gastric cancer cell growth and migration. It also induces apoptosis by affecting key molecular pathways, showing therapeutic potential for gastric cancer treatment.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Gastric cancer presents a significant global health challenge, particularly in China, with advanced stages having poor prognoses.
- Novel therapeutic strategies are crucial for improving survival rates in gastric cancer patients.
- Demethylzeylasteral, derived from Tripterygium wilfordii, has demonstrated anticancer properties, but its specific effects on gastric cancer require elucidation.
Purpose of the Study:
- To investigate the antitumor effects of demethylzeylasteral on human gastric cancer cells.
- To explore the underlying molecular mechanisms of demethylzeylasteral's action in gastric cancer.
Main Methods:
- Cell Counting Kit-8 and colony formation assays to assess proliferation.
- Transwell assay to evaluate cell migration.
- Flow cytometry to analyze apoptosis and mitochondrial membrane potential.
- Western blotting to examine protein expression and phosphorylation levels (ERK1/2, AKT, GSK-3β, Bcl-2, Bax, caspases, PARP).
Main Results:
- Demethylzeylasteral significantly inhibited gastric cancer cell proliferation and migration in a dose-dependent manner.
- Treatment induced apoptosis and reduced mitochondrial membrane potential in gastric cancer cells.
- Demethylzeylasteral downregulated ERK1/2, AKT, and GSK-3β phosphorylation, decreased Bcl-2 expression, and increased Bax, cleaved caspase-3, cleaved caspase-9, and cleaved PARP expression.
Conclusions:
- Demethylzeylasteral demonstrates significant therapeutic potential against gastric cancer.
- The compound exerts its effects by inhibiting proliferation, migration, and inducing apoptosis through modulation of key signaling pathways and apoptosis-related proteins.
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