Role of Caspases, Bax and Bcl-2 in Chrysin-Induced Apoptosis in the A549 Human Lung Adenocarcinoma Epithelial Cells
Saeed Samarghandian, Mohsen Azimi Nezhad and Gholamreza Mohammadi
Affiliation: Department of Basic Medical sciences, Neyshabur University of Medical Sciences, Neyshabur, Iran.
Objectives: 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.
Materials & 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 ± 0.8μM 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.
Conclusion: 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.
Keywords: Apoptosis, Bax, Bcl-2, caspases, chrysin, lung cancer.
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