Collaborative Drug Discovery Research (CDDR) Group, Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia.
Phytomedicine. 2012 May 15;19(7):609-17. doi: 10.1016/j.phymed.2012.01.007. Epub 2012 Mar 6.
Endophytic fungi have been shown to be a promising source of biologically active natural products. In the present study, extracts of four endophytic fungi isolated from plants of the National Park, Pahang were evaluated for their cytotoxic activity and the nature of their active compounds determined. Those extracts exhibiting activity with IC(50) values less than 17 μg/ml against HCT116, MCF-7 and K562 cell lines were shown to induce apoptosis in these cell lines. Molecular analysis, based on sequences of the rDNA internal transcribed spacers ITS1 and ITS4, revealed all four endophytic fungi to be ascomycetes: three sordariomycetes and a dothideomycete. Six known compounds, cytochalasin J, dechlorogriseofulvin, demethylharzianic-acid, griseofulvin, harzianic acid and 2-hexylidene-3-methyl-succinic acid were identified from a rapid dereplication technique for fungal metabolites using an in-house UV library. The results from the present study suggest the potential of endophytic fungi as cytotoxic agents, and there is an indication that the isolates contain bioactive compounds that mainly kill cancer cells by apoptosis.
内生真菌已被证明是具有生物活性天然产物的有前途的来源。在本研究中，评估了从彭亨国家公园植物中分离出的四种内生真菌的提取物的细胞毒性活性，并确定了其活性化合物的性质。那些对 HCT116、MCF-7 和 K562 细胞系表现出 IC50 值小于 17μg/ml 的活性的提取物，被证明能诱导这些细胞系的细胞凋亡。基于 rDNA 内部转录间隔区 ITS1 和 ITS4 的序列的分子分析表明，所有四种内生真菌都是子囊菌：三种腔孢菌和一种尾孢菌。从使用内部 UV 文库的真菌代谢物快速去重复技术中，从六种已知化合物（细胞松弛素 J、去氯灰黄菌素、去甲基哈茨木素、灰黄霉素、哈茨木素和 2-己烯基-3-甲基琥珀酸）中鉴定出。本研究的结果表明内生真菌作为细胞毒性剂的潜力，并且有迹象表明分离物含有主要通过细胞凋亡杀死癌细胞的生物活性化合物。
