Induction of Apoptosis in Tumor Cells by Three Naphthoquinone Esters Isolated from Thai Medicinal Plant : Rhinacanthus nasutus KURZ(Pharmacognosy)
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概要
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Rhinacanthus nasutus KURZ. (Acanthaceae) has been used as Thai traditional medicine for the treatment of various cancers. Recently, we reported that rhinacanthins, active components of the plant, had antiproliferative activity against human cancer line cells. In the present study, we investigated the growth inhibitory mechanism of rhinacanthins-C, -N and -Q, three main naphthoquinone esters isolated from the roots of R. nasutus KURZ. in human cervical carcinoma (HeLaS3) cells by means of TUNEL staining, DNA fragmentation assay, flow cytometry, and cleavage assay of Asp-Glu-Val-Asp-peptide-nitroanilide, a caspase-3 substrate. After the HeLaS3 cells was exposed with different concentrations of the drugs, rhinacanthins-C, -N and -Q exhibited antiproliferative effects on HeLaS3 cells with the IC_<50> values of 80, 65, 73μM; 55, 45, 55μM; and 1.5, 1.5 and 5.0μM for 24, 48 and 72h time points, respectively. Morphological changes showing nuclear fragmentation of rhinacanthins-treated cells were clearly observed after 48h exposure. Consistent with this observation, the appearance of a ladder formation was also evident with an agarose gel electrophoresis of the extracted DNA. Flow cytometric analysis revealed that rhinacanthin-N caused G2/M arrest of HeLaS3 cells after 24h incubation, and increased the proportion of sub-G1 hypodiploid cells, apoptotic cells, in the population of HeLaS3 cells after 48 and 72h incubation. Moreover, the drug treatment markedly elevated the activity of caspase-3. Based on these results, our findings demonstrated for the first time that the inhibitory effects of three main naphthoquinone esters isolated from the roots of R. nasutus KURZ. on the growth of HeLaS3 cells appear to arise from the induction of apoptosis, that might be associated with the activation of caspase-3 pathway.
- 公益社団法人日本薬学会の論文
- 2006-10-01
著者
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ASAI Tomohiro
Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry, and
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OKU Naoto
Department of Radiobiochemistry, School of Pharmaceutical Sciences, University of Shizuoka
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奥 直人
Dep. Of Medical Biochemistry School Of Pharmaceutical Sciences Univ. Of Shizuoka
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Oku Naoto
静岡県立大学 薬学部
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奥 直人
静岡県立大学大学院薬学研究科
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奥 直人
静岡県立大学 薬学部 医薬生命化学教室
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Oku N
Univ. Shizuoka Shizuoka Jpn
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Shimizu K
Department Of Pharmaceutics Hoshi University
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Oku Naoto
Department Of Medical Biochemistry And Coe Program In The 21st Century University Of Shizuoka School
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Asai Tomohiro
Department Of Medical Biochemistry And Global Coe University Of Shizuoka School Of Pharmaceutical Sc
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Asai T
Department Of Medical Biochemistry And Coe Program In The 21st Century University Of Shizuoka School
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Asai Tomohiro
Department Of Cardiovascular Surgery Okayama University Graduate School Of Medicine Dentistry And Ph
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YONEZAWA Sei
Department of Medical Biochemistry, University of Shizuoka School of Pharmaceutical Sciences
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Asai Tomohiro
Department Of Medical Biochemistry University Of Shizuoka School Of Pharmaceutical Sciences
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SHIMIZU Kosuke
Department of Medical Biochemistry and COE Program in the 21st Century, School of Pharmaceutical Sci
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Ruchirawat Somsak
Lab. Of Medicinal Chemistry Chulabhorn Res. Inst.
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Yonezawa Sei
Department Of Medical Biochemistry And Coe Program In The 21st Century School Of Pharmaceutical Scie
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Yonezawa S
Department Of Medical Biochemistry University Of Shizuoka School Of Pharmaceutical Sciences
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Shimizu Kosuke
Department Of Medical Biochemistry University Of Shizuoka School Of Pharmaceutical Sciences
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奥 直人
静岡県立大学薬学部医薬生命科学教室
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SIRIPONG Pongpun
Natural Products Research Section, Research Division, National Cancer Institute
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YAHUAFAI Jantana
Natural Products Research Section, Research Division, National Cancer Institute
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ICHIKAWA Kanae
Department of Medical Biochemistry and COE Program in the 21th Century, Graduate School of Pharmaceu
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KANOKMEDAKUL Kwanjai
Department of Chemistry, Khon Kaen University
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RUCHIRAWAT Somsak
Laboratory of Medicinal Chemistry, Chulabhorn Research Institute
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ICHIKAWA Kanae
University of Shizuoka School of Pharmaceutical Sciences
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Ichikawa Kanae
Department Of Medical Biochemistry And Coe Program In The 21st Century School Of Pharmaceutical Scie
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Ruchirawat Somsak
Laboratory Of Medicinal Chemistry Chulabhorn Research Institute
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Kanokmedhakul Kwanjai
Fac. Of Sci. Khon Kaen Univ.
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Kanokmedakul Kwanjai
Department Of Chemistry Khon Kaen University
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Yahuafai Jantana
Natural Products Research Section Research Division National Cancer Institute
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Siripong Pongpun
Res. Div. National Cancer Inst. Thailand
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Siripong Pongpun
Natural Product Research Section Research Division National Cancer Institute
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OKU Naoto
Department of Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University
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