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对森林植物内生真菌进行生物勘探,寻找具有抗癌潜力的生物活性代谢产物。

Bioprospecting endophytic fungi of forest plants for bioactive metabolites with anticancer potentials.

作者信息

El-Sayed El-Sayed R, Kloc Magdalena, Kulbacka Julita, Choromańska Anna, Bielecka Monika, Strzała Tomasz, Łyczko Jacek, Boratyński Filip

机构信息

Department of Food Chemistry and Biocatalysis, Wrocław University of Environmental and Life Sciences, Norwida 25, 50-375, Wrocław, Poland.

Plant Research Department, Nuclear Research Center, Egyptian Atomic Energy Authority, Cairo, Egypt.

出版信息

Sci Rep. 2025 Jul 21;15(1):26423. doi: 10.1038/s41598-025-10372-9.

DOI:10.1038/s41598-025-10372-9
PMID:40691195
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12280201/
Abstract

Cancer continues to be a major cause of mortality worldwide, emphasizing the critical need for innovative and more effective anticancer drugs with enhanced efficacy and minimal side effects. In response, researchers have begun investigating the largely unexplored metabolites produced by fungal endophytes for the development of novel therapeutics. In this regard, the present work aims to assess the anticancer potential of the fungal endophytes of forest plants (local forest in Wrocław, Poland), which remains yet unexamined. Fungal endophytes were isolated from their host plants, purified, grown and their extracts were separately prepared from cell-free culture media and biomass. The prepared extracts were tested for their cytotoxic potentials against human melanoma, breast adenocarcinoma, lung carcinoma, and normal cell lines using the MTT-based assay. Cultures of these isolates were exposed to several doses of Co gamma rays to study their effects on the cytotoxic potential of their cell-based and extracellular extracts against the beforementioned cell lines. Preparative thin-layer chromatography fractionation followed by GC-MS were applied to identify compounds in the active fractions. Five fungi, namely Penicillium yarmokense JAR-L1 (leaves of Sorbus aucuparia), Penicillium sp. sp. BRZ-B (bark of Betula pendula), Fusarium avenaceum KLON-B (bark of Acer platanoides), Penicillium charlesii SOS-B1 (bark of Pinus sylvestris), and Umbelopsis isabellina COR-L2 (leaves of Corylus avellana) showed high toxicity with increased specificity for cancer cells rather than healthy cells. Exposure to gamma rays at specific doses enhanced the cytotoxic potentials of extracts of these fungi. Bioactive compounds in the active bands after prep-TLC were identified. Some of the identified compounds from active fractions such as squalene, fenchone, α-phellandrene, p-Cymene, α-thujone, and 18-norabietane are being reported for the first time from fungal cultures. The findings of this study indicate that endophytic fungi may represent a promising and untapped reservoir of bioactive compounds with cytotoxic effects which opens new avenues for scientific exploration and could contribute to the advancement of novel anticancer therapeutics.

摘要

癌症仍然是全球主要的死亡原因,这凸显了对创新且更有效的抗癌药物的迫切需求,这类药物需具备更高的疗效和最小的副作用。作为回应,研究人员已开始研究真菌内生菌产生的基本上未被探索的代谢产物,以开发新型治疗方法。在这方面,目前的工作旨在评估森林植物(波兰弗罗茨瓦夫当地森林)的真菌内生菌的抗癌潜力,而这一潜力尚未得到研究。从其宿主植物中分离出真菌内生菌,进行纯化、培养,并分别从无细胞培养基和生物量中制备提取物。使用基于MTT的检测方法,测试所制备的提取物对人黑色素瘤、乳腺腺癌、肺癌和正常细胞系的细胞毒性潜力。将这些分离株的培养物暴露于几剂钴伽马射线,以研究其对基于细胞的提取物和细胞外提取物针对上述细胞系的细胞毒性潜力的影响。采用制备型薄层色谱分离,随后进行气相色谱 - 质谱联用,以鉴定活性馏分中的化合物。五种真菌,即雅莫肯青霉JAR - L1(花楸树叶)、青霉属sp. sp. BRZ - B(垂枝桦树皮)、燕麦镰刀菌KLON - B(挪威槭树皮)、查尔斯青霉SOS - B1(欧洲赤松树皮)和伊莎贝林伞霉COR - L2(榛树叶)表现出高毒性,对癌细胞的特异性高于健康细胞。以特定剂量暴露于伽马射线可增强这些真菌提取物的细胞毒性潜力。鉴定了制备型薄层色谱后活性条带中的生物活性化合物。从活性馏分中鉴定出的一些化合物,如角鲨烯、小茴香酮、α - 水芹烯、对伞花烃、α - 侧柏酮和18 - 去甲枞烷,首次从真菌培养物中被报道。本研究的结果表明,内生真菌可能代表了一个有前景且未被开发的具有细胞毒性作用的生物活性化合物库,这为科学探索开辟了新途径,并可能有助于新型抗癌治疗方法的进步。

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本文引用的文献

1
Bioprospecting endophytic fungi of forest plants for their monoamine oxidase A and cholinesterases inhibitors, and peroxisome proliferator-activated receptor gamma agonists.对森林植物内生真菌进行生物勘探,寻找其单胺氧化酶A和胆碱酯酶抑制剂以及过氧化物酶体增殖物激活受体γ激动剂。
J Appl Microbiol. 2025 Mar 3;136(3). doi: 10.1093/jambio/lxaf034.
2
Tumour evolution and microenvironment interactions in 2D and 3D space.二维和三维空间中的肿瘤进化和微环境相互作用。
Nature. 2024 Oct;634(8036):1178-1186. doi: 10.1038/s41586-024-08087-4. Epub 2024 Oct 30.
3
Bioprospecting Endophytic Fungi of Forest Plants for Bioactive Metabolites with Antibacterial, Antifungal, and Antioxidant Potentials.
从森林植物内生真菌中寻找具有抗菌、抗真菌和抗氧化潜力的生物活性代谢产物。
Molecules. 2024 Oct 8;29(19):4746. doi: 10.3390/molecules29194746.
4
Novel nanoconjugates of metal oxides and natural red pigment from the endophyte Monascus ruber using solid-state fermentation.新型金属氧化物纳米缀合物和来源于内生真菌红曲 Monascus ruber 的天然红色素,采用固态发酵法制备。
Microb Cell Fact. 2024 Sep 29;23(1):259. doi: 10.1186/s12934-024-02533-8.
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Enhancing bioprocessing of red pigment from immobilized culture of gamma rays mutant of the endophytic fungus Monascus ruber SRZ112.强化红曲霉菌SRZ112γ射线突变体固定化培养产红色素的生物工艺。
J Biol Eng. 2024 Aug 15;18(1):44. doi: 10.1186/s13036-024-00439-y.
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Endophytic fungi: A future prospect for breast cancer therapeutics and drug development.内生真菌:乳腺癌治疗与药物开发的未来前景
Heliyon. 2024 Jul 4;10(13):e33995. doi: 10.1016/j.heliyon.2024.e33995. eCollection 2024 Jul 15.
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BMC Microbiol. 2024 Jun 8;24(1):200. doi: 10.1186/s12866-024-03337-x.
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Arch Microbiol. 2024 Feb 26;206(3):122. doi: 10.1007/s00203-024-03829-4.
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