Catalase Contents in Cells Determine Sensitivity to the Apoptosis Inducer Gallic Acid
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概要
- 論文の詳細を見る
Gallic acid(3, 4, 5-trihydroxybenzoic acid, GA)is known to induce apoptosis in cancer cells at lower IC_<50> values compared with values for normal cells. Apoptosis is inhibited completely by the addition of conditioned medium from cultured hepatocytes, whereas it is not prevented by conditioned media from tumor cells. We therefore studied the reason for the different response to GA-induced apoptosis. GA-induced dRLh-84 cell death was completely abolished by the addition of peroxisome or cytosol as well as conditoned medium from primary cultured rat hepatocyte. As GA-induced cell death is known to be mediated by reactive oxygen species(ROS)and intracellular Ca^<2+> we determined the type of ROS generated by GA and found that GA generated hydrogen peroxide in culture medium. The addition of hydrogen peroxide generated by GA induced cell death in dRLh-84 cells. These results suggest that GA-induced cell death is mediated by hydrogen peroxide. On the other hand, the inhibitory activity of hepatocyte medium on GA-induced cell death was completely abolished by anti-catalase antibody. When the amount of catalase antigen was determined by Western blotting analysis, conditoned medium and the cytoplasm of hepatocytes contained high concentrations of catalase. Conditioned media from various tumor cell lines did not contain catalase, and the cytoplasm contained only low levels of catalase. These results show that GA-sensitive cells, including various tumor cells, produce only small amounts of catalase and secreted little enzyme into media, suggesting a lack of protective machinery against GA. In contrast, GA-insensitive cells, including hepatocytes, produce large amounts of catalase and release it in medium, resulting in the development of insensitivity to GA. In conclusion, catalase contents in cells determine different sensitivity to GA.
- 公益社団法人日本薬学会の論文
- 2001-09-01
著者
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Inoue Makoto
名古屋市立大学 薬研究生薬学
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Inoue M
Lab. Of Medicinal Resources School Of Pharmacy Aichi Gakuin Univ.
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OGIHARA Yukio
Nihon Pharmaceutical University
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Ogihara Y
Nihon Pharmaceutical University
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Ogihara Yukio
Laboratory Of Pharmacognosy Graduate School Of Pharmaceutical Sciences Nagoya City University
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Ogihara Yukio
Faculty Of Pharmacy Meijo Universitv
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Ogihara Yukio
Department Of Pharmacognosy Faculty Of Pharmaceutical Sciences Nagoya City University
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Ogihara Yukio
Graduate School Of Pharmaceutical Sciences Nagoya City University
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Inoue M
Laboratory Of Pharmacognosy Graduate School Of Pharmaceutical Sciences Nagoya City University
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INOUE Makoto
Laboratory of Pharmacognosy, Graduate School of Pharmaceutical Sciences, Nagoya City University
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ISUZUGAWA Kazuto
Laboratory of Pharmacognosy, Graduate School of Pharmaceutical Sciences, Nagoya City University
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Isuzugawa Kazuto
Department Of Pharmacognosy Faculty Of Pharmaceutical Sciences Nagoya City University
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Ogihara Y
Department Of Pharmacognosy And Plant Chemistry Faculty Of Pharmaceutical Sciences Nagoya City Unive
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Inoue Makoto
Laboratory Of Metabolic Biochemistry Faculty Of Agriculture Tottori University
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Inoue Makoto
Laboratory of Medicinal Resources, School of Pharmacy, Aichi Gakuin University
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Isuzugawa Kazuto
Laboratory of Animal Breeding, The University of Tokyo
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