論文 - 詳細
| RRC ID | 77882 |
|---|---|
| 著者 | Kikuchi T, Uchiyama E, Ukiya M, Tabata K, Kimura Y, Suzuki T, Akihisa T. |
| タイトル | Cytotoxic and apoptosis-inducing activities of triterpene acids from Poria cocos. |
| ジャーナル | J Nat Prod |
| Abstract |
Six lanostane-type triterpene acids (1a-6a), isolated from Poria cocos , and their methyl ester (1b-6b) and hydroxy derivatives (1c-6c) were prepared. Upon evaluation of the cytotoxic activity of these compounds against leukemia (HL60), lung (A549), melanoma (CRL1579), ovary (NIH:OVCAR-3), breast (SK-BR-3), prostate (DU145), stomach (AZ521), and pancreas (PANC-1) cancer cell lines, 11 compounds (5a, 6a, 2b-5b, 1c, and 3c-6c) exhibited activity with single-digit micromolar IC(50) values against one or more cell lines. Poricotriol A (1c), a hydroxy derivative of poricoic acid A (1a), exhibited potent cytotoxicities against six cell lines with IC(50) values of 1.2-5.5 μM. Poricotriol A induced typical apoptotic cell death in HL60 and A549 cells on evaluation of the apoptosis-inducing activity by flow cytometric analysis. Western blot analysis in HL60 cells showed that poricotriol A activated caspases-3, -8, and -9, while increasing the ratio of Bax/Bcl-2. This suggested that poricotriol A induced apoptosis via both mitochondrial and death receptor pathways in HL60. On the other hand, poricotriol A did not activate caspases-3, -8, and -9, but induced translocation of apoptosis-inducing factor (AIF) from mitochondria and increased the ratio of Bax/Bcl-2 in A549. This suggested that poricotriol A induced apoptosis via the mitochondrial pathway mostly by translocation of AIF, independent from the caspase pathway in A549. Furthermore, poricotriol A was shown to possess high selective toxicity in lung cancer cells since it exhibited only weak cytotoxicity against a normal lung cell line (WI-38). |
| 巻・号 | 74(2) |
| ページ | 137-44 |
| 公開日 | 2011-2-25 |
| DOI | 10.1021/np100402b |
| PMID | 21250700 |
| MeSH | Antineoplastic Agents / chemistry Antineoplastic Agents / isolation & purification* Antineoplastic Agents / pharmacology* Apoptosis Inducing Factor / chemistry Apoptosis Inducing Factor / isolation & purification Apoptosis Inducing Factor / pharmacology* Caspases / metabolism Drug Screening Assays, Antitumor Female HL-60 Cells Humans Inhibitory Concentration 50 Male Molecular Structure Poria / chemistry* Triterpenes / chemistry Triterpenes / isolation & purification* Triterpenes / pharmacology* |
| IF | 3.782 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | WI-38(RCB0702) |