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Phthalides Isolated from the Endolichenic Arthrinium sp. EL000127 Exhibits Antiangiogenic Activity.

ABSTRACT: Endolichenic fungi (ELF) produce specialized metabolites that have various medicinal properties. Inhibition of tumor angiogenesis efficaciously suppresses many types of cancer. This study aimed to discover novel antiangiogenic agents from specialized metabolite extracts of ELF strains isolated from Korean lichens. The EtOAc extracts of 51 ELF strains were subjected to a screening pipeline consisting of cell viability, scratch wound healing, and Transwell migration assays. The EtOAc extract of Arthrinium sp. EL000127 showed the most potent inhibitory activity against the chemotactic migration of human umbilical vein endothelial cells (HUVEC). Targeted isolation on the major LC-MS peaks exhibited a previously known phthalide, 3-O-methylcyclopolic acid (1), and two unknown analogues of 1, 3-O-phenylethylcyclopolic acid (2) and 3-O-p-hydroxyphenylethylcyclopolic acid (3). The structures were characterized by MS and NMR analyses. All the isolates were acquired and applied to bioassays as racemates due to spontaneous racemization. Among the isolates, compound 3 effectively inhibits HUVEC motility by suppressing mRNA expressions of genes regulating epithelial cell survival and motility, which suggested that compound 3 is a potent antiangiogenic agent suitable for further exploration as a potential novel therapeutic against cancers.

SUBMITTER: Gamage CDB

PROVIDER: S-EPMC10077456 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Phthalides Isolated from the Endolichenic <i>Arthrinium</i> sp. EL000127 Exhibits Antiangiogenic Activity.

Gamage Chathurika D B CDB Lee Kyungha K Park So-Yeon SY Varlı Mücahit M Lee Chang Wook CW Kim Seong-Min SM Zhou Rui R Pulat Sultan S Yang Yi Y Taş İsa İ Hur Jae-Seoun JS Kang Kyo Bin KB Kim Hangun H

ACS omega 20230321 13

Endolichenic fungi (ELF) produce specialized metabolites that have various medicinal properties. Inhibition of tumor angiogenesis efficaciously suppresses many types of cancer. This study aimed to discover novel antiangiogenic agents from specialized metabolite extracts of ELF strains isolated from Korean lichens. The EtOAc extracts of 51 ELF strains were subjected to a screening pipeline consisting of cell viability, scratch wound healing, and Transwell migration assays. The EtOAc extract of <i ...[more]

PMID: 37033794

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Project description:Microorganisms thrive in extreme environments and are known for synthesizing valuable metabolites. Salt-loving microorganisms can flourish in saline environments which inhibit the growth of other microbial life, and they possess the potential to produce stable and novel biomolecules for the use in biotechnological applications, including anticancer compounds. Sambhar Lake is the largest inland soda lake in India and is an appropriate habitat for halophilic bacterial and archaeal strains in terms of diversity and potential production of bioactive compounds. In the present study, a moderately halo-alkaliphilic bacterial strain C12A1 was isolated from Sambhar Lake, located in Rajasthan, India. C12A1 was gram-positive, motile, rod-shaped, formed oval endospores, produced carotenoids, and exhibited optimal growth at 37 °C in 10⁻15% NaCl (pH 8). C12A1 was found to be able to hydrolyze skimmed milk, gelatin, and Tween 80 but unable to hydrolyze starch and carboxymethylcellulose. C12A1 showed 98.87% and 98.50% identity in 16S rRNA gene sequence to P. halophilus and P. salipiscarius, respectively. Nevertheless, C12A1 was clustered within the clade consisting of P. salipiscarius strains, but it showed a distinct lineage. Thus, C12A1 was designated as Piscibacillus sp. Cell proliferation assay results showed that C12A1 broth extract (BEP) decreased cell viability in breast cancer MDA-MB-231 cells, which was confirmed by the MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assay. Induction of cell toxicity was visualized by microscopy. Reverse Transcriptase PCR (RT-PCR) analysis demonstrated that BEP inhibited the expression of proliferative B-cell lymphoma-extra large (Bcl-xL) and cell cycle marker Cyclin-dependent kinase 2 (CDK2) at transcript levels. Similarly, cell migration and colony formation along with mesenchymal marker vimentin and stem cell marker BMI transcripts were found to be inhibited when cells were treated with the BEP. The anti-breast cancer potential of C12A1 indicates that microorganisms inhabiting saline-alkaline habitats, with Piscibacillus sp. in particular, are a promising source for discovery of novel bioactive substances.

Dataset Information

Phthalides Isolated from the Endolichenic Arthrinium sp. EL000127 Exhibits Antiangiogenic Activity.

Publications

Phthalides Isolated from the Endolichenic <i>Arthrinium</i> sp. EL000127 Exhibits Antiangiogenic Activity.

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