Involvement of catalase in the apoptotic mechanism induced by apigenin in HepG2 human hepatoma cells

• Published in: Chemico-biological interactions Vol. 193; no. 2; pp. 180 - 189
• Main Authors: Valdameri, Glaucio, Trombetta-Lima, Marina, Worfel, Paulo R., Pires, Amanda R.A., Martinez, Glaucia R., Noleto, Guilhermina R., Cadena, Silvia M.S.C., Sogayar, Mari C., Winnischofer, Sheila M.B., Rocha, Maria E.M.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 05.09.2011
• Subjects: Animals; antioxidant activity; antioxidants; Antioxidants - pharmacology; Apigenin; Apigenin - pharmacology; Apoptosis; Apoptosis - drug effects; Apoptosis - physiology; Biocatalysis - drug effects; Catalase; Catalase - genetics; Catalase - metabolism; Catalase - pharmacology; Cell Size - drug effects; Cell Survival - drug effects; cell viability; Cells, Cultured; Cytochromes c - metabolism; DNA Fragmentation - drug effects; Gene Expression - drug effects; Gene Expression - genetics; Glutathione - metabolism; Glutathione Peroxidase - genetics; Glutathione Peroxidase - metabolism; Glutathione Reductase - genetics; Glutathione Reductase - metabolism; Hep G2 Cells; Hepatocytes; Hepatocytes - cytology; Hepatocytes - drug effects; hepatoma; HepG2 cells; human cell lines; Humans; Hydrogen Peroxide - pharmacology; Male; messenger RNA; Mice; Mice, Inbred Strains; Reactive Oxygen Species - metabolism; Superoxide Dismutase - genetics; Superoxide Dismutase - metabolism; toxicity; HepG2 cells; Hepatocytes; Catalase; Apigenin; Apoptosis
• ISSN: 0009-2797; 1872-7786
• DOI: 10.1016/j.cbi.2011.06.009

► Antioxidant enzymes in the apoptotic mechanism induced by apigenin in HepG2 cells. ► Catalase downregulation play an essential role in apigenin-induced apoptosis. ► Catalase added to the culture medium partially protected apigenin-induced cell death. ► Direct involvement of H2O2 in the apoptotic mechanism induced by apigenin. ► Apigenin promotes GSH depletion and ROS generation, contributing to apoptosis. 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 H2O2-dependent pathway via reduction of the antioxidant defenses.