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Polyketides isolated from an endophyte Penicillium oxalicum 2021CDF-3 inhibit pancreatic tumor growth

Fungal secondary metabolites are inherently considered valuable resources for new drugs discovery. To search for novel fungal secondary metabolites with lead compounds potential, a fungal strain Penicillium oxalicum 2021CDF-3, an endophyte of the marine red algae Rhodomela confervoides, was chemical...

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Autores principales: Weng, Wenya, Li, Ruidian, Zhang, Yanxia, Pan, Xiaofu, Jiang, Shicui, Sun, Chuchu, Zhang, Chi, Lu, Xuemian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9549284/
https://www.ncbi.nlm.nih.gov/pubmed/36225350
http://dx.doi.org/10.3389/fmicb.2022.1033823
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author Weng, Wenya
Li, Ruidian
Zhang, Yanxia
Pan, Xiaofu
Jiang, Shicui
Sun, Chuchu
Zhang, Chi
Lu, Xuemian
author_facet Weng, Wenya
Li, Ruidian
Zhang, Yanxia
Pan, Xiaofu
Jiang, Shicui
Sun, Chuchu
Zhang, Chi
Lu, Xuemian
author_sort Weng, Wenya
collection PubMed
description Fungal secondary metabolites are inherently considered valuable resources for new drugs discovery. To search for novel fungal secondary metabolites with lead compounds potential, a fungal strain Penicillium oxalicum 2021CDF-3, an endophyte of the marine red algae Rhodomela confervoides, was chemically studied. Cultivation of this fungus on solid rice medium yielded 10 structurally diverse metabolites (1–10), including two new polyketides, namely oxalichroman A (1) and oxalihexane A (2). Their structures were determined by detailed analysis of NMR and HRESIMS spectroscopic data. Oxalihexane A (2) was elucidated as a novel polyketide formed by a cyclohexane and cyclohexanone moiety via an ether bond. The stereochemistry of 2 was successfully assigned by NMR and ECD calculations. In the cytotoxic assay, the new compound 2 showed remarkable inhibitory effect on the human pancreatic cancer PATU8988T cell line. Further pharmacological study demonstrated that the expression level of Cyclin D1 was down-regulated by the treatment with 2, which suggested that cell cyclin abnormity was involved in pancreatic tumor cell apoptosis. Moreover, the activation of Wnt5a/Cyclin D1 signaling pathway might be involved in the mechanism of panreatic tumor cell apoptosis induced by 2.
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spelling pubmed-95492842022-10-11 Polyketides isolated from an endophyte Penicillium oxalicum 2021CDF-3 inhibit pancreatic tumor growth Weng, Wenya Li, Ruidian Zhang, Yanxia Pan, Xiaofu Jiang, Shicui Sun, Chuchu Zhang, Chi Lu, Xuemian Front Microbiol Microbiology Fungal secondary metabolites are inherently considered valuable resources for new drugs discovery. To search for novel fungal secondary metabolites with lead compounds potential, a fungal strain Penicillium oxalicum 2021CDF-3, an endophyte of the marine red algae Rhodomela confervoides, was chemically studied. Cultivation of this fungus on solid rice medium yielded 10 structurally diverse metabolites (1–10), including two new polyketides, namely oxalichroman A (1) and oxalihexane A (2). Their structures were determined by detailed analysis of NMR and HRESIMS spectroscopic data. Oxalihexane A (2) was elucidated as a novel polyketide formed by a cyclohexane and cyclohexanone moiety via an ether bond. The stereochemistry of 2 was successfully assigned by NMR and ECD calculations. In the cytotoxic assay, the new compound 2 showed remarkable inhibitory effect on the human pancreatic cancer PATU8988T cell line. Further pharmacological study demonstrated that the expression level of Cyclin D1 was down-regulated by the treatment with 2, which suggested that cell cyclin abnormity was involved in pancreatic tumor cell apoptosis. Moreover, the activation of Wnt5a/Cyclin D1 signaling pathway might be involved in the mechanism of panreatic tumor cell apoptosis induced by 2. Frontiers Media S.A. 2022-09-26 /pmc/articles/PMC9549284/ /pubmed/36225350 http://dx.doi.org/10.3389/fmicb.2022.1033823 Text en Copyright © 2022 Weng, Li, Zhang, Pan, Jiang, Sun, Zhang and Lu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Weng, Wenya
Li, Ruidian
Zhang, Yanxia
Pan, Xiaofu
Jiang, Shicui
Sun, Chuchu
Zhang, Chi
Lu, Xuemian
Polyketides isolated from an endophyte Penicillium oxalicum 2021CDF-3 inhibit pancreatic tumor growth
title Polyketides isolated from an endophyte Penicillium oxalicum 2021CDF-3 inhibit pancreatic tumor growth
title_full Polyketides isolated from an endophyte Penicillium oxalicum 2021CDF-3 inhibit pancreatic tumor growth
title_fullStr Polyketides isolated from an endophyte Penicillium oxalicum 2021CDF-3 inhibit pancreatic tumor growth
title_full_unstemmed Polyketides isolated from an endophyte Penicillium oxalicum 2021CDF-3 inhibit pancreatic tumor growth
title_short Polyketides isolated from an endophyte Penicillium oxalicum 2021CDF-3 inhibit pancreatic tumor growth
title_sort polyketides isolated from an endophyte penicillium oxalicum 2021cdf-3 inhibit pancreatic tumor growth
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9549284/
https://www.ncbi.nlm.nih.gov/pubmed/36225350
http://dx.doi.org/10.3389/fmicb.2022.1033823
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