β -Asarone Increases Chemosensitivity by Inhibiting Tumor Glycolysis in Gastric Cancer.
EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE(2020)
Abstract
beta-asarone is the main active ingredient of the Chinese herb Rhizoma Acori Tatarinowii, which exhibits a wide range of biological activities. It was confirmed to be an efficient cytotoxic agent against gastroenteric cancer cells. However, the exact mechanism of beta-asarone in gastric cancer (GC) remains to be elucidated. The present study showed the inhibitory effect of beta-asarone on three types of different differentiation stage GC cell lines (MGC803, SGC7901, and MKN74) in a dose-dependent manner. Meanwhile, the synergistic sensitivity of beta-asarone and cisplatin was confirmed by using the median-effect principle. Flow cytometry assay revealed that under both normoxia and CoCl2-induced hypoxia conditions, beta-asarone can induce apoptosis of GC cells, which can block GC cells in the cell cycle G2/M phase, showing obvious subdiploid peak. Moreover, the activity of lactic dehydrogenase (LDH), an enzyme that plays an important role in the final step of tumor glycolysis, was significantly decreased in GC cells following treatment with beta-asarone. Mechanistically, beta-asarone can reduce pyruvate dehydrogenase kinase (PDK) 1, phospho(p)-PDK1, PDK4, hypoxia-inducible factor 1-alpha (HIF1 alpha), c-myc, STAT5, and p-STAT5 expression, which revealed how beta-asarone affects tumor glycolysis. In conclusion, the present study provided evidence in support of the hypothesis that the increase of chemotherapy sensitization by beta-asarone is associated with the inhibition of tumor glycolysis.
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Key words
chemosensitivity,gastric cancer,tumor glycolysis
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