文章基本信息

标题：Induction of Apoptosis in Tumor Cells by Three Naphthoquinone Esters Isolated from Thai Medicinal Plant: Rhinacanthus nasutus KURZ.
本地全文：下载
作者：Pongpun Siripong ; Jantana Yahuafai ; Kosuke Shimizu 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2006
卷号：29
期号：10
页码：2070-2076
DOI：10.1248/bpb.29.2070
出版社：The Pharmaceutical Society of Japan
摘要：Rhinacanthus nasutus K URZ . (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 K URZ . 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 IC₅₀ values of 80, 65, 73 μ M ; 55, 45, 55 μ M ; and 1.5, 1.5 and 5.0 μ M for 24, 48 and 72 h time points, respectively. Morphological changes showing nuclear fragmentation of rhinacanthins-treated cells were clearly observed after 48 h 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 24 h incubation, and increased the proportion of sub-G1 hypodiploid cells, apoptotic cells, in the population of HeLaS3 cells after 48 and 72 h 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 K URZ . 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.
关键词：Rhinacanthus nasutus;naphthoquinone ester;rhinacanthin;antitumor activity;apoptosis;caspase-3 activation