EGCG induces apoptosis in human laryngeal epidermoid carcinoma Hep2 cells via mitochondria with the release of apoptosis-inducing factor and endonuclease G.
ABSTRACT (-)-Epigallocatechin-3-gallate (EGCG), a major green tea polyphenol, was tested for in vitro cytotoxicity against human laryngeal epidermoid carcinoma of the larynx Hep2 cells. EGCG-induced apoptotic cell death accompanied by a change in the cell cycle. However, EGCG did not result in caspase activation, nor did a caspase inhibitor block cell death. Furthermore, EGCG caused no change in the intracellular levels of reactive oxygen species (ROS). The levels of p53 were increased in the EGCG-treated cells, with a corresponding decrease in Bcl-2 and Bid protein levels as well as an increase in the Bax level. In addition, EGCG induced the cytoplasmic release of cytochrome c from the mitochondria accompanied by a decreased mitochondrial membrane potential, and subsequently upregulated translocation of apoptosis-inducing factor (AIF) and endonuclease G (EndoG) into the nucleus during the apoptotic process. Taken together, these findings indicate that the p53-mediated mitochondrial pathway and the nuclear translocation of AIF and EndoG play a crucial role in EGCG-induced apoptosis of human laryngeal epidermoid carcinoma Hep2 cells, which proceeds through a caspase-independent pathway.
Article: Tea in chemoprevention of cancer.[show abstract] [hide abstract]
ABSTRACT: This review summarizes available information on epidemiological and experimental data showing an association of tea consumption with cancer prevention. Studies showing cancer risk associated with tea consumption are also summarized. Tea is grown in about 30 countries and, next to water, is the most widely consumed beverage in the world. Experimental studies demonstrating the chemopreventive effects of tea have been conducted principally with green tea; limited studies have also assessed the usefulness of black tea. Majority of these studies have been carried out in skin tumor model system where consumption through drinking water of water extracts of tea or a polyphenolic fraction isolated from tea has been shown to afford protection against chemical carcinogen- or ultraviolet radiation-induced skin tumorigenesis. Tea consumption has also been shown to afford protection against chemical carcinogen-induced lung, forestomach, esophagus, duodenum, pancreas, liver, breast and colon carcinogenesis in specific bioassay models. Evidence has also accumulated showing that tea polyphenols prevent tumor promoter- and ultraviolet B-induced inflammatory responses in murine skin. The species and strains of animals, dose, route, frequency and duration of carcinogen administration, as well as types, route of administration and duration of tea or its polyphenolic component(s) treatment are described in detail. A brief description regarding mechanism(s) responsible for the broad chemopreventive effects of tea is provided. Epidemiologic studies, though inconclusive, in general suggest a possible preventive effect of tea consumption on human cancer. On the basis of available information, epidemiologic and experimental studies are ongoing to draw the possible relationship between tea consumption and cancer causation and prevention. Appropriate strategies for future clinical chemoprevention trials to translate animal data to human cancer risk are warranted.International Journal of Oncology 02/1996; 8(2):221-38. · 2.66 Impact Factor
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ABSTRACT: Flavonoids have antioxidant and antitumor promoting effects. Rhus verniciflua Stokes (RVS) is a flavonoid-rich herbal medicine that has long been used in Korea as both a food additive and antitumor agent. It was previous reported that a purified flavonoid fraction prepared from RVS, herein named RCMF (the RVS chloroform-methanol fraction), inhibited the proliferation and induced apoptosis in human osteosarcoma (HOS) cells. This study examined the mechanisms involved in the RCMF-mediated apoptosis in HOS cells. RCMF was shown to be capable of inducing apoptosis in HOS cells by inducing p53 in the cells resulting in the decrease in Bcl-2 level, activation of Bax, and cytoplasmic release of cytochrome c, which led to the translocation of apoptosis-inducing factor (AIF) and endonuclease G (EndoG) into the nucleus. However, the RCMF-induced apoptosis was suppressed by transfecting the cells with antisense p53 oligonucleotides but not by treating them with a MAPK or caspase inhibitor. This suppression occurred through the regulation of Bcl-2 members as well as by preventing the nuclear translocation of the mitochondrial apoptogenic factors. Overall, it appears that p53-mediated mitochondrial stress and the nuclear translocation of AIF and EndoG are mainly required for the apoptosis induced by RCMF.APOPTOSIS 08/2007; 12(7):1289-98. · 3.95 Impact Factor
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ABSTRACT: Leber's hereditary optic neuropathy (LHON) is associated with mitochondrial DNA point mutations affecting different subunits of complex I. By replacing glucose with galactose in the medium, cybrids harboring each of the three LHON pathogenic mutations (11778/ND4, 3460/ND1, 14484/ND6) suffered a profound ATP depletion over a few hours and underwent apoptotic cell death, which was caspase-independent. Control cybrids were unaffected. In addition to cytochrome c, apoptosis inducing factor (AIF) and endonuclease G (EndoG) were also released from the mitochondria into the cytosol in LHON cybrids, but not in control cells. Exposure of isolated nuclei to cytosolic fractions from LHON cybrids maintained in galactose medium caused nuclear fragmentation, which was strongly reduced by immuno-depletion with anti-AIF and anti-EndoG antibodies. In conclusion, the caspase-independent death of LHON cybrids incubated in galactose medium is triggered by rapid ATP depletion and mediated by AIF and EndoG.APOPTOSIS 11/2005; 10(5):997-1007. · 3.95 Impact Factor