Persimmon Leaf Extract Inhibits the ATM Activity during DNA Damage Response Induced by Doxorubicin in A549 Lung Adenocarcinoma Cells
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概要
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Persimmon leaf (PL) has been commonly recognized for its wide variety of health benefits. A previous study has reported that persimmon leaf extract (PLE) contained flavonols with the 2″-galloly moiety (PLEg). Galloylated homologues generically show stronger activity in their biological function, so enhanced functions can be expected for PLEg. We investigated in this present study the effect of PLEg on the cellular DNA damage checkpoint signaling to sensitize cancer chemotherapy. Treatment with PLE and PLEg significantly increased the cytotoxicity of doxorubicin (DOX) in A549 adenocarcinoma cells. PLE and PLEg reduced the phosphorylation of checkpoint proteins such as structural maintenance of chromosomes 1 (SMC1), checkpoint kinase 1 (Chk1), and p53 in DOX-treated cells. Moreover, PLE decreased the phosphorylation of ATM (ataxia telangiectasia mutated) in a dose-dependent manner. PLE, and especially PLEg, abrogated the G2/M checkpoint during DOX-induced DNA damage. These results suggest that PLEg specifically inhibited ATM-dependent checkpoint activation by DOX, and that PLEg might be a useful sensitizer in cancer chemotherapy.
- 2011-04-23
著者
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Nishida Hiroshi
Department Of Cardiology Regeneration Medicine And Bioethics Gifu University Graduate School Of Medi
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Konishi T
Faculty Of Pharmaceutical Sciences Niigata University Of Pharmacy And Applied Life Sciences
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Konishi Tetsuya
Department Of Applied Life Sciences Niigata University Of Pharmacy And Applied Life Sciences
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Nakajima Yuki
Department Of Applied Life Sciences Niigata University Of Pharmacy And Applied Life Sciences
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TATEWAKI Naoto
Department of Applied Life Sciences, Niigata University of Pharmacy and Applied Life Sciences
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Hirayama Masao
Department Of Food Science Niigata University Of Pharmacy And Applied Life Science
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Nakajima Yuki
Dep. Of Food Sci. Niigata Univ. Of Pharmacy And Applied Life Sciences
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KAWAKAMI Kayoko
Department of Food Science, Niigata University of Pharmacy and Applied Life Science
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Nishida Hiroshi
Department Of Food Science Niigata University Of Pharmacy And Applied Life Sciences
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Kawakami Kayoko
Department Of Food Science Niigata University Of Pharmacy And Applied Life Sciences
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Nishida Hiroshi
Department Of Applied Life Sciences Niigata University Of Pharmacy And Applied Life Sciences
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Tatewaki Naoto
Department Of Food Science Niigata University Of Pharmacy And Applied Life Sciences
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Hirayama Masao
Department Of Food Science Faculty Of Applied Life Sciences Niigata University Of Pharmacy And Applied Life Sciences (nupals):bourbon Corporation
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Nakajima Yuki
Department of Applied Chemistry, Faculty of Engineering, Saitama University, 255 Shimo-okubo, Sakura, Saitama 338-8570, Japan
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