Hyperoside induces both autophagy and apoptosis in non small cell lung cancer cells in vitro
Aim:Hyperoside (quercetin 3 O b D galactopyranoside) is a flavonol glycoside found in plants of the genera Hypericum and Crataegus, which exhibits anticancer, anti oxidant, and anti inflammatory activities. In this study we investigated whether autophagy was involved in the anticancer mechanisms of hyperoside in human non small cell lung cancer cells in vitro.Methods:Human non small cell lung cancer cell line A549 was tested, and human bronchial epithelial cell line BEAS 2B was used for comparison. The expression of LC3 II, apoptotic and signaling proteins was measured using Western blotting. Autophagosomes were observed with MDC staining, LC3 immunocytochemistry, and GFP LC3 fusion protein techniques. Cell viability was assessed using MTT assay.Results:Hyperoside (0.5, 1, 2 mmol/L) dose dependently increased the expression of LC3 II and autophagosome numbers in A549 cells, but had no such effects in BEAS 2B cells. Moreover, hyperoside dose dependently inhibited the phosphorylation of Akt, mTOR, p70S6K and 4E BP1, but increased the phosphorylation of ERK1/2 in A549 cells. Insulin (200 nmol/L) markedly enhanced the phosphorylation of Akt and decreased LC3 II expression in A549 cells, which were reversed by pretreatment with hyperoside, whereas the MEK1/2 inhibitor U0126 (20 mmol/L) did not blocked hyperoside induced LC3 II expression. Finally, hyperoside dose dependently suppressed the cell viability and induced apoptosis in A549 cells, which were significantly attenuated by pretreatment with the autophagy inhibitor 3 methyladenine (2.5 mmol/L).Conclusion:Hyperoside induces both autophagy and apoptosis in human non small cell lung cancer cells in vitro. The autophagy is induced through inhibiting the Akt/mTOR/p70S6K signal pathways, which contributes to anticancer actions of hyperoside.
Acta Pharmacologica Sinica