title: Gallic acid induces apoptosis via caspase-3 and mitochondrion-dependent pathways in vitro and suppresses lung xenograft tumor growth in vivo.
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 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 Ca(2+) production, the loss of mitochondrial membrane potential (DeltaPsi(m)), and caspase-3 activation. The efficacious induction of apoptosis and DNA damage was observed at 50-500 microM 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 DeltaPsi(m) 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.
authors.affiliation: Division of Chest Medicine, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan.
authors.forename: Bin-Chuan
authors.initials: BC
authors.lastname: Ji
authors.forename: Wu-Huei
authors.initials: WH
authors.lastname: Hsu
authors.forename: Jai-Sing
authors.initials: JS
authors.lastname: Yang
authors.forename: Te-Chun
authors.initials: TC
authors.lastname: Hsia
authors.forename: Chi-Cheng
authors.initials: CC
authors.lastname: Lu
authors.forename: Jo-Hua
authors.initials: JH
authors.lastname: Chiang
authors.forename: Jiun-Long
authors.initials: JL
authors.lastname: Yang
authors.forename: Ching-Hsiung
authors.initials: CH
authors.lastname: Lin
authors.forename: Jen-Jyh
authors.initials: JJ
authors.lastname: Lin
authors.forename: Lee-Jen Wu
authors.initials: LJ
authors.lastname: Suen
authors.forename: Wellington
authors.initials: W
authors.lastname: Gibson Wood
authors.forename: Jing-Gung
authors.initials: JG
authors.lastname: Chung
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000503:physiopathology; D053148:Caspase 3 / Q000378:metabolism*; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects*; D000091342:Endoplasmic Reticulum Chaperone BiP; D005707:Gallic Acid / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000503:physiopathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014183:Transplantation, Heterologous; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; C000717248:Hspa5 protein, mouse; D051028:bcl-2-Associated X Protein; D005707:Gallic Acid; D053148:Caspase 3