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Anti-Cancer Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)
ISSN (Print): 1871-5206
ISSN (Online): 1875-5992
Epub Abstract Ahead of Print
DOI: 10.2174/1871520614666140209144042      Price:  $95









Role of Caspases, Bax and Bcl-2 in Chrysin-Induced Apoptosis in the A549 Human Lung Adenocarcinoma Epithelial Cells

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Author(s): Saeed Samarghandian, Mohammad Bagher Delkhosh, Gholamreza Mohammadi and Mohammadreza Taghavi
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Abstract:
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 ± 0.8M at 48 and 72 h, respectively. Reactivity with annexin V fluorescence antibody and propidium iodide showed that chrysin induced apoptosis in 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 lung cancer cells by inducing cancer cell apoptosis via regulation of the Bcl-2 family and also activation of caspase-3 and -9, which may, in part, explain its anticancer activity
Affiliation:
Department of Basic Medical sciences, Neyshabur University of Medical Sciences, Neyshabur, Iran