Mitochondrial Targeting in an Anti-Austerity Approach Involving Bioactive Metabolites Isolated from the Marine-Derived Fungus Aspergillus sp
Autor: | John Refaat Fahim, Masayoshi Arai, Mostafa A. Fouad, Mohamed Kamel, Waleed A Abdel-Naime, Atsushi Kimishima, Andi Setiawan |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
Pharmaceutical Science
Fungus 03 medical and health sciences mitochondrial electron transport chain 0302 clinical medicine nutrient starvation Drug Discovery medicine cancer physcion lcsh:QH301-705.5 Pharmacology Toxicology and Pharmaceutics (miscellaneous) 030304 developmental biology 0303 health sciences Aspergillus Tumor microenvironment marine-derived Aspergillus sp biology Chemistry Cancer medicine.disease biology.organism_classification Electron transport chain Phenotype microenvironment austerity Sponge lcsh:Biology (General) Biochemistry 030220 oncology & carcinogenesis Cancer cell |
Zdroj: | Marine Drugs Volume 18 Issue 11 Marine Drugs, Vol 18, Iss 555, p 555 (2020) |
ISSN: | 1660-3397 |
DOI: | 10.3390/md18110555 |
Popis: | The tumor microenvironment is a nutrient-deficient region that alters the cancer cell phenotype to aggravate cancer pathology. The ability of cancer cells to tolerate nutrient starvation is referred to as austerity. Compounds that preferentially target cancer cells growing under nutrient-deficient conditions are being employed in anti-austerity approaches in anticancer drug discovery. Therefore, in this study, we investigated physcion (1) and 2-(2&prime 3-epoxy-1&prime 3&prime 5&prime heptatrienyl)-6-hydroxy-5-(3-methyl-2-butenyl) benzaldehyde (2) obtained from a culture extract of the marine-derived fungus Aspergillus species (sp.), which were isolated from an unidentified marine sponge, as anti-austerity agents. The chemical structures of 1 and 2 were determined via spectroscopic analysis and comparison with authentic spectral data. Compounds 1 and 2 exhibited selective cytotoxicity against human pancreatic carcinoma PANC-1 cells cultured under glucose-deficient conditions, with IC50 values of 6.0 and 1.7 µ M, respectively. Compound 2 showed higher selective growth-inhibitory activity (505-fold higher) under glucose-deficient conditions than under general culture conditions. Further analysis of the mechanism underlying the anti-austerity activity of compounds 1 and 2 against glucose-starved PANC-1 cells suggested that they inhibited the mitochondrial electron transport chain. |
Databáze: | OpenAIRE |
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