2001年9月1日
61(P-18) Fusarium属が生産する新規抗腫瘍剤lucilactaeneに関する研究(ポスター発表の部)
天然有機化合物討論会講演要旨集
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- 巻
- 号
- 43
- 開始ページ
- 359
- 終了ページ
- 364
- 記述言語
- 日本語
- 掲載種別
- DOI
- 10.24496/tennenyuki.43.0_359
- 出版者・発行元
- 天然有機化合物討論会
Inactivation of tumor suppressor protein p53 is the most common alteration found in human cancer. Therefore, the small molecules that induce a cell cycle arrest or apoptosis p53-independently or allow mutant p53 to maintain an active form might be a good candidate for anticancer drugs of various types of cancers. During the extensive screening, we found that a fungal strain, Fusarium sp. RK97-94, produced a new cell cycle inhibitor, lucilactaene, that arrested the cell cycle progression at the G1 phase at 37℃ in H1299/tsp53 cells. The transfectant H1299/tsp53 stably expresses a temperature-sensitive (Ala138>Val) human p53 in H1299 cells (human non-small cell lung cancer cells) which adopts the transcriptionally inactive, mutant conformation at the non-permissive temperature of 37℃, but behaves as a wild-type at the permissive temperature of 32℃. The structure of lucilactaene (C_<22>H_<27>NO_6) was elucidated by high-resolution MS spectrum, NMR experiments including several 2D-NMR methods, and other spectroscopic analysis. Lucilactaene has a hexahydro-3a-hydroxy-5-oxo-2H-furo[3,2-b]pyrrol-6-yl ring system with a hydrophobic side chain such as fusarin A, a non-mutagenic metabolite of Fusarium moniliforme. Lucilactaene is also structurally similar to epolactaene and NG-391, which were previously reported as the neuritogenic and the neuronal cell-protecting molecules, respectively. Lucilactaene (5μg/ml) significantly augmentated the G1 population of H1299/tsp53 cells after a 24h-incubation at 37℃. In addition, lucilactaene also significantly activated the p21^<WAF1> promoter, a target of the p53 gene, in H1299/tsp53-luc cells, which was established by transfecting H1299/tsp53 cells with a luciferase reporter gene linked at the 3' of the human p21^<WAF1> promoter. Detailed studies on various kinds of cancer cell lines and the mode of action of lucilactaene are also now being undertaken.
- リンク情報
- ID情報
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- DOI : 10.24496/tennenyuki.43.0_359
- CiNii Articles ID : 110006682106
- CiNii Books ID : AN00154136