title: Role of caspases, Bax and Bcl-2 in chrysin-induced apoptosis in the A549 human lung adenocarcinoma epithelial cells.
abstract: OBJECTIVE
  Honey is reported to contain various compounds such as antioxidants. Chrysin is a natural and biologically active compound extracted from honey. It possesses antioxidant properties and promotes cell death by perturbing cell cycle progression. We focused on the possible role that chrysin may act as a potential anticancer agent, and tested its biological activity and possible mechanisms in the human lung adenocarcinoma epithelial cell line.
  
  
  METHODS
  Antiproliferative effect of honey and chrysin were determined by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay; DNA fragmentation was determined by gel electrophoresis assay; apoptosis was detected by flow cytometer; apoptosis-related gene expression was detected by reverse transcription polymerase chain reaction assay; and activation of caspase-3 and caspase-9 were evaluated by a colorimetric assay; Bax and Bcl-2 protein expression were also analysed by western blotting.
  
  
  RESULTS
  The results revealed that the cell viability decreased in a concentration- and time- dependent manner in the malignant cells treated with honey and chrysin in comparison with the nonmalignant cells. The IC50 values of honey against A549 cells were determined 15 ± 0.05% and 8 ± 0.05 % after 48 and 72h, respectively. The IC50 dose of chrysin was determined to be 49.2 ± 0.6 and 38.7 ± 0.8 μM at 48 and 72 h, respectively. Reactivity with Annexin V fluorescence antibody and propidium iodide showed that chrysin induced apoptosis in the lung cancer cells (p<0.001). Moreover, chrysin treatment resulted in the activation of caspase-3 and - 9 and an increase in the Bax/Bcl-2 ratio (p<0.01). Bax protein expression was increased but Bcl-2 protein expression decreased in chrysin-treated cells .Chrysin inhibits the growth of the lung cancer cells by inducing cancer cell apoptosis via the regulation of the Bcl-2 family and also activation of caspase-3 and -9, which may, in part, explain its anticancer activity.
  
  
  CONCLUSIONS
  This study shows that chrysin could also be considered as a promising chemotherapeutic agent and anticancer activity in treatment of the lung cancer cells in future.
authors: Saeed
authors: S
authors: Samarghandian
authors: Mohsen Azimi
authors: MA
authors: Nezhad
authors: Department of Basic Medical sciences, Neyshabur University of Medical Sciences, Neyshabur, Iran. samarghandians@mums.ac.ir.
authors: Gholamreza
authors: G
authors: Mohammadi
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004847:Epithelial Cells / Q000187:drug effects* / Q000473:pathology; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; C494826:BAX protein, human; D005419:Flavonoids; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C043561:chrysin; D020169:Caspases