title: Hyperoside induces both autophagy and apoptosis in non-small cell lung cancer cells in vitro.
abstract: OBJECTIVE
  Hyperoside (quercetin-3-O-β-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 μmol/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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Special Requirement Wards, First Affiliated Hospital of Soochow University, Suzhou 215006, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Fu
authors.affiliation: Department of Special Requirement Wards, First Affiliated Hospital of Soochow University, Suzhou 215006, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Liaoning Medical University, Jinzhou 121001, China.
authors.forename: Xiang-nan
authors.initials: XN
authors.lastname: Jin
authors.affiliation: Department of Pharmacology, Liaoning Medical University, Jinzhou 121001, China.
authors.forename: Hai-juan
authors.initials: HJ
authors.lastname: Sui
authors.affiliation: Department of Pharmacology, Liaoning Medical University, Jinzhou 121001, China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Liaoning Medical University, Jinzhou 121001, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Jin
mesh_terms: D000072283:A549 Cells; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011794:Quercetin / Q000031:analogs & derivatives* / Q000494:pharmacology; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; C021304:hyperoside; D011794:Quercetin