An Endolichenic Fungi-Derived Fatty Acid, cis-10-Nonadecenoic acid, Suppresses Colorectal Cancer Stemness.

IF 3.2 3区医学 Q2 PHARMACOLOGY & PHARMACY

Biomolecules & Therapeutics Pub Date : 2025-09-01 Epub Date: 2025-08-06 DOI:10.4062/biomolther.2025.062

Mücahit Varlı, Eun-Young Lee, So-Yeon Park, Yi Yang, Prima F Hillman, Rui Zhou, Jae-Seoun Hur, Sang-Jip Nam, Hangun Kim

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引用次数: 0

Abstract

Endolichenic fungi (ELF), symbionts of lichens, have been reported to produce diverse bioactive secondary metabolites with promising pharmaceutical potential. In this study, we isolated and identified an ELF, EL001668 (KACC 83020BP), from Cetraria laevigata Rass., and assessed its crude extract and bioactive compounds against colorectal cancer (CRC) stem cell activity. cis-10-nonadecenoic acid (c-NDA), isolated through bioactivity-guided fractionation exerted substantial inhibitory effects on CRC stemness, such as the suppression of spheroid formation and the downregulation of the key stem cell markers ALDH1, CD44, and CD133. Comparative analysis with the omega-3 fatty acids EPA and DHA, with well-established properties, showed that c- NDA exerted comparable or superior inhibitory effects against the markers and phenotypic traits of stemness. Besides, the crude extract of EL001668 exhibited greater suppression of certain markers in comparison to the individual compounds. These findings suggest that c-NDA, in conjunction with ELF-derived compounds, holds potential as a novel therapeutic candidate targeting CRC stem cells. Taken together, the current study demonstrated that c-NDA, similar to EPA and DHA, may possess adjunct or complementary effects in cancer treatment and other diseases.

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一种内生真菌衍生的脂肪酸，顺式-10-壬烯酸，抑制结直肠癌的发生。

地衣内生真菌（ELF）是地衣的共生体，据报道可以产生多种具有生物活性的次生代谢物，具有广阔的药用潜力。本研究分离并鉴定了一株来自白蚕（Cetraria laevigata Rass）的ELF基因EL001668 （KACC 83020BP）。研究了其粗提物及其生物活性成分对结直肠癌（CRC）干细胞活性的影响。通过生物活性引导分离分离得到的顺式-10-壬烯酸（c-NDA）对结直肠癌的干性具有明显的抑制作用，如抑制球状体的形成和下调干细胞关键标志物ALDH1、CD44和CD133。与具有良好特性的omega-3脂肪酸EPA和DHA的对比分析表明，c- NDA对茎秆的标记物和表型性状具有相当或更好的抑制作用。此外，与单个化合物相比，EL001668粗提物对某些标记物的抑制作用更大。这些发现表明，c-NDA与elf衍生化合物结合，具有作为靶向结直肠癌干细胞的新型治疗候选药物的潜力。综上所述，目前的研究表明，c-NDA与EPA和DHA类似，可能在癌症和其他疾病的治疗中具有辅助或补充作用。

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来源期刊

Biomolecules & Therapeutics 医学-药学

CiteScore

6.60

自引率

8.10%

发文量

审稿时长

6-12 weeks

期刊介绍： Biomolecules & Therapeutics (Biomolecules & Therapeutics) (Print ISSN 1976-9148, Online ISSN 2005-4483) is an international, peer-reviewed, open access journal that covers pharmacological and toxicological fields related to bioactive molecules and therapeutics. It was launched in 1993 as "The Journal of Applied Pharmacology (ISSN 1225-6110)", and renamed "Biomolecules & Therapeutics" (Biomol Ther: abbreviated form) in 2008 (Volume 16, No. 1). It is published bimonthly in January, March, May, July, September and November. All manuscripts should be creative, informative, and contribute to the development of new drugs. Articles in the following categories are published: review articles and research articles.