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Gallic Acid Induces Apoptosis via Caspase-3 and Mitochondrion-Dependent Pathways in Vitro and Suppresses Lung Xenograft Tumor Growth in Vivo

Several studies have shown that gallic acid (GA) induces apoptosis in different cancer cell lines, whereas the mechanism of action of GA-induced apoptosis at the molecular level in human non-small-cell lung cancer NCI-H460 cells is not well-known. Here, GA decreasing the percentage of viable NCI-H46...

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Published in:Journal of agricultural and food chemistry 2009-08, Vol.57 (16), p.7596-7604
Main Authors: Ji, Bin-Chuan, Hsu, Wu-Huei, Yang, Jai-Sing, Hsia, Te-Chun, Lu, Chi-Cheng, Chiang, Jo-Hua, Yang, Jiun-Long, Lin, Ching-Hsiung, Lin, Jen-Jyh, Suen, Lee-Jen Wu, Gibson Wood, Wellington, Chung, Jing-Gung
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Language:English
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Summary:Several studies have shown that gallic acid (GA) induces apoptosis in different cancer cell lines, whereas the mechanism of action of GA-induced apoptosis at the molecular level in human non-small-cell lung cancer NCI-H460 cells is not well-known. Here, GA decreasing the percentage of viable NCI-H460 cells was investigated; GA-induced apoptosis involved G2/M phase arrest and intracellular Ca2+ production, the loss of mitochondrial membrane potential (ΔΨm), and caspase-3 activation. The efficacious induction of apoptosis and DNA damage was observed at 50−500 μM for 24 and/or 48 h as examined by flow cytometry, DAPI staining, and Comet assay methods. Western blotting and flow cytometric analysis also demonstrated that GA increased protein levels of GADD153 and GRP78, activation of caspase-8, -9, and -3, loss of ΔΨm and cytochrome c, and AIF release from mitochondria. Moreover, apoptosome formation and activation of caspase cascade were associated with apoptotic cell death. GA increased Bax and Bad protein levels and decreased Bcl-2 and Bcl-xL levels. GA may also induce apoptosis through a caspase-independent AIF pathway. In nude mice bearing NCI-H460 xenograft tumors, GA inhibited tumor growth in vivo. The data suggest that GA induced apoptosis in NCI-H460 lung cancer cells via a caspase-3 and mitochondrion-dependent pathway and inhibited the in vivo tumor growth of NCI-H460 cells in xenograft models.
ISSN:0021-8561
1520-5118
DOI:10.1021/jf901308p