Tags

Type your tag names separated by a space and hit enter

Acacetin induces apoptosis in human gastric carcinoma cells accompanied by activation of caspase cascades and production of reactive oxygen species.
J Agric Food Chem. 2005 Feb 09; 53(3):620-30.JA

Abstract

Acacetin (5,7-dihydrocy-4'-methoxy flavone), which is a flavonoid compound, possesses anti-peroxidative and anti-inflammatory effects. The effects of acacetin on cell viability in human gastric carcinoma AGS cells were investigated. This study demonstrated that acacetin was able to inhibit cell proliferation and induce apoptosis in a concentration- and time-dependent manner. Acacetin-induced cell death was characterized with changes in nuclear morphology, DNA fragmentation, and cell morphology. The molecular mechanism of acacetin-induced apoptosis was also investigated. Treatment with acacetin caused induction of caspase-3 activity in a time-dependent manner, but not caspase-1 activity, and induced the degradation of DNA fragmentation factor (DFF-45) and poly(ADP-riobse) polymerase. Cell death was completely prevented by a pancaspase inhibitor, Z-Val-Ala-Asp-fluoromethyl ketone. Furthermore, treatment with acacetin caused a rapid loss of mitochondrial transmembrane potential, stimulation of reactive oxygen species (ROS), release of mitochondrial cytochrome c into cytosol, and subsequent induction of procaspase-9 processing. Antioxidants such as N-acetylcysteine and catalase, but not superoxide dismutase, allopurinol, or pyrrolidine dithiocarbamate, significantly inhibited acacetin-induced cell death. In addition, it was found that acacetin promoted the up-regulation of Fas and FasL prior to the processing and activation of pro-caspase-8 and cleavage of Bid, suggesting the involvement of a Fas-mediated pathway in acacetin-induced apoptosis. On the other hand, the results showed that acacetin-induced apoptosis was accompanied by up-regulation of Bax and p53, down-regulation of Bcl-2, and cleavage of Bad. Taken together, these results suggest that ROS production and a certain intimate link might exist between receptor- and mitochondria-mediated death signalings that committed to acacetin-induced apoptosis in AGS cells. The induction of apoptosis by acacetin may provide a pivotal mechanism for its cancer chemopreventive action.

Authors+Show Affiliations

Department of Seafood Science, National Kaohsiung Marine University, No. 142 Hai-Chuan Road, Nan-Tzu, Kaohsiung, Taiwan. mhpan@maill.nkmu.edu.twNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15686411

Citation

Pan, Min-Hsiung, et al. "Acacetin Induces Apoptosis in Human Gastric Carcinoma Cells Accompanied By Activation of Caspase Cascades and Production of Reactive Oxygen Species." Journal of Agricultural and Food Chemistry, vol. 53, no. 3, 2005, pp. 620-30.
Pan MH, Lai CS, Hsu PC, et al. Acacetin induces apoptosis in human gastric carcinoma cells accompanied by activation of caspase cascades and production of reactive oxygen species. J Agric Food Chem. 2005;53(3):620-30.
Pan, M. H., Lai, C. S., Hsu, P. C., & Wang, Y. J. (2005). Acacetin induces apoptosis in human gastric carcinoma cells accompanied by activation of caspase cascades and production of reactive oxygen species. Journal of Agricultural and Food Chemistry, 53(3), 620-30.
Pan MH, et al. Acacetin Induces Apoptosis in Human Gastric Carcinoma Cells Accompanied By Activation of Caspase Cascades and Production of Reactive Oxygen Species. J Agric Food Chem. 2005 Feb 9;53(3):620-30. PubMed PMID: 15686411.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Acacetin induces apoptosis in human gastric carcinoma cells accompanied by activation of caspase cascades and production of reactive oxygen species. AU - Pan,Min-Hsiung, AU - Lai,Ching-Shu, AU - Hsu,Ping-Chi, AU - Wang,Ying-Jan, PY - 2005/2/3/pubmed PY - 2005/3/23/medline PY - 2005/2/3/entrez SP - 620 EP - 30 JF - Journal of agricultural and food chemistry JO - J Agric Food Chem VL - 53 IS - 3 N2 - Acacetin (5,7-dihydrocy-4'-methoxy flavone), which is a flavonoid compound, possesses anti-peroxidative and anti-inflammatory effects. The effects of acacetin on cell viability in human gastric carcinoma AGS cells were investigated. This study demonstrated that acacetin was able to inhibit cell proliferation and induce apoptosis in a concentration- and time-dependent manner. Acacetin-induced cell death was characterized with changes in nuclear morphology, DNA fragmentation, and cell morphology. The molecular mechanism of acacetin-induced apoptosis was also investigated. Treatment with acacetin caused induction of caspase-3 activity in a time-dependent manner, but not caspase-1 activity, and induced the degradation of DNA fragmentation factor (DFF-45) and poly(ADP-riobse) polymerase. Cell death was completely prevented by a pancaspase inhibitor, Z-Val-Ala-Asp-fluoromethyl ketone. Furthermore, treatment with acacetin caused a rapid loss of mitochondrial transmembrane potential, stimulation of reactive oxygen species (ROS), release of mitochondrial cytochrome c into cytosol, and subsequent induction of procaspase-9 processing. Antioxidants such as N-acetylcysteine and catalase, but not superoxide dismutase, allopurinol, or pyrrolidine dithiocarbamate, significantly inhibited acacetin-induced cell death. In addition, it was found that acacetin promoted the up-regulation of Fas and FasL prior to the processing and activation of pro-caspase-8 and cleavage of Bid, suggesting the involvement of a Fas-mediated pathway in acacetin-induced apoptosis. On the other hand, the results showed that acacetin-induced apoptosis was accompanied by up-regulation of Bax and p53, down-regulation of Bcl-2, and cleavage of Bad. Taken together, these results suggest that ROS production and a certain intimate link might exist between receptor- and mitochondria-mediated death signalings that committed to acacetin-induced apoptosis in AGS cells. The induction of apoptosis by acacetin may provide a pivotal mechanism for its cancer chemopreventive action. SN - 0021-8561 UR - https://www.unboundmedicine.com/medline/citation/15686411/Acacetin_induces_apoptosis_in_human_gastric_carcinoma_cells_accompanied_by_activation_of_caspase_cascades_and_production_of_reactive_oxygen_species_ L2 - https://doi.org/10.1021/jf048430m DB - PRIME DP - Unbound Medicine ER -