title: Involvement of catalase in the apoptotic mechanism induced by apigenin in HepG2 human hepatoma cells.
abstract: Apigenin has been reported to inhibit proliferation of cancer cells; however, the mechanism underlying its action is not completely understood. Here, we evaluated the effects of apigenin on the levels of expression and activity of antioxidant enzymes, and the involvement of ROS in the mechanism of cell death induced by apigenin in HepG2 human hepatoma cells. Upon treatment with apigenin, HepG2 cells displayed a reduction in cell viability in a dose- and time-dependent manner, and some morphological changes. In addition, apigenin treatment induced ROS generation and significantly decreased the mRNA levels and activity of catalase and levels of intracellular GSH. On the other hand, apigenin treatment did not alter the expression or activity levels of other antioxidant enzymes. Addition of exogenous catalase significantly reduced the effects of apigenin on HepG2 cell death. We also demonstrated that HepG2 cells are more sensitive to apigenin-mediated cell death than are primary cultures of mouse hepatocytes, suggesting a differential toxic effect of this agent in tumor cells. Our results suggest that apigenin-induced apoptosis in HepG2 cells may be mediated by a H(2)O(2)-dependent pathway via reduction of the antioxidant defenses.
authors.affiliation: Department of Biochemistry and Molecular Biology, Federal University of Paraná, Curitiba, PR, Brazil.
authors.forename: Glaucio
authors.initials: G
authors.lastname: Valdameri
authors.forename: Marina
authors.initials: M
authors.lastname: Trombetta-Lima
authors.forename: Paulo R
authors.initials: PR
authors.lastname: Worfel
authors.forename: Amanda R A
authors.initials: AR
authors.lastname: Pires
authors.forename: Glaucia R
authors.initials: GR
authors.lastname: Martinez
authors.forename: Guilhermina R
authors.initials: GR
authors.lastname: Noleto
authors.forename: Silvia M S C
authors.initials: SM
authors.lastname: Cadena
authors.forename: Mari C
authors.initials: MC
authors.lastname: Sogayar
authors.forename: Sheila M B
authors.initials: SM
authors.lastname: Winnischofer
authors.forename: Maria E M
authors.initials: ME
authors.lastname: Rocha
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D047310:Apigenin / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D055162:Biocatalysis / Q000187:drug effects; D002374:Catalase / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D048429:Cell Size / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D005980:Glutathione Reductase / Q000235:genetics / Q000378:metabolism; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000094765:Glutathione Peroxidase GPX1
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D047310:Apigenin; D045304:Cytochromes c; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005978:Glutathione; D000094765:Glutathione Peroxidase GPX1