A Potent Apoptosis-Inducing Activity of a Sesquiterpene Lactone, Arucanolide, in HL60 Cells : a Crucial Role of Apoptosis-Inducing Factor
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概要
- 論文の詳細を見る
Six main sesquiterpene lactones (germacranolides) from Calea urticifolia were evaluated for in vitro cytotoxicity against human tumor cell lines HL60 and SW480 cells. Among them, arucanolide and parthenolide displayed marked cytotoxicity against both cell lines. Arucanolide exhibited a low IC50 in HL60 cells. The cytotoxic activity of arucanolide was observed at lower concentrations compared to that of parthenolide, which has been reported to be a typical and simple germacranolide. The activity was found to be mainly due to apoptosis that was assessed by morphological findings, DNA ladder formation (24 – 36 h), and flow cytometric analysis in HL60 cells. Western blotting and an apoptosis inhibition assay using caspase inhibitors did not demonstrate the activation of any caspases tested. However, the mitochondrial membrane potential of HL60 cells was lost after 24-h treatment with arucanolide, and concurrently apoptosis-inducing factor (AIF) released from mitochondria was detected by Western blot analysis. The inactivation of nuclear factor-κB, which has been commonly shown in parthenolide-induced apoptosis, did not occur in arucanolide-induced apoptosis. Taken together, the findings presented here indicate that arucanolide induced marked apoptosis in HL60 cells mainly by dissipating mitochondrial membrane potential, which would trigger AIF-induced apoptosis.
- 社団法人 日本薬理学会の論文
- 2005-02-20
著者
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Iinuma Munekazu
Dep. Of Bioactive Molecules Pharmacognosy Gifu Pharmaceutical Univ.
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Iinuma M
Gifu Pharmaceutical University
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Iinuma Munekazu
岐阜薬科大学
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Nozawa Yoshinori
Gifu International Institute of Biotechnology
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AKAO Yukihiro
Gifu International Institute of Biotechnology
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NAKAGAWA Yoshihito
Gifu International Institute of Biotechnology
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Matsuura Nobuyasu
Department Of Life Science Faculty Of Science Okayama University Of Science
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Akao Y
Gifu International Institute Of Biotechnology
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Nozawa Y
Gifu International Institute Of Biotechnology
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IINUMA Munekazu
Pharmacognosy, Department of Public Health Pharmacy, Gifu Pharmaceutical University
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YI Kong
Gifu International Institute of Biotechnology
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NAOI Makoto
Gifu International Institute of Biotechnology
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NAKAYAMA Toshihiro
Gifu Shellac Manufacturing Co., Ltd.
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Iinuma Munekazu
Gifu Prefectural Institute Of Health And Environment
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Iinuma Munekazu
Gifu Prefectural Institute Of Health And Environmental Sciences
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Araki Yoko
Nagaragawa Res. Center Api Co. Ltd.
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Araki Yoko
Nagaragawa Research Center Api Co. Ltd.
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Iinuma Munekazu
Pharmacognosy Department Of Public Health Pharmacy Gifu Pharmaceutical University
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Naoi M
Gifu International Institute Of Biotechnology
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Nakayama Toshihiro
Gifu Shellac Manufacturing Co. Ltd.
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