Gallic Acid Induces Apoptosis via Caspase-3 and Mitochondrion-Dependent Pathways in Vitro and Suppresses Lung Xenograft Tumor Growth in Vivo http://pubs.acs.org

J. I. Bin-Chuan, Wu Huei Hsu, Jai Sing Yang, Te Chun Hsia, Chi Cheng Lu, Jo Hua Chiang, Jiun Long Yang, Ching Hsiung Lin, L. Jen-jyh, Wu Suen Lee-jen, Gibson Wood Wellington, Jing Gung Chung

Research output: Contribution to journalArticlepeer-review

165 Scopus citations

Abstract

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 nonsmall-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

Original languageEnglish (US)
Pages (from-to)7596-7604
Number of pages9
JournalJournal of agricultural and food chemistry
Volume57
Issue number16
DOIs
StatePublished - Sep 23 2009

Keywords

  • Apoptosis
  • Caspase-3
  • Gallic acid
  • Mitochondria membrane potential (Δψ)
  • Nci-h460 lung cancer cells
  • Xenograft tumors

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