Abdel-Naime, Waleed A and Kimishima, Atsushi and Setiawan, Andi and Fahim, John Refaat and Fouad, Mostafa A. and Kamel, Mohamed Salah and Arai, Masayoshi Mitochondrial Targeting in an Anti-Austerity Approach Involving Bioactive Metabolites Isolated from the Marine-Derived Fungus Aspergillus sp. MDPI Multidisciplinary Digital Publishing Institute.
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Abstract
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′,3-epoxy-1′,3′,5′-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 µM, 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
| Item Type: | Other |
|---|---|
| Subjects: | Q Science > Q Science (General) |
| Depositing User: | Prof Andi Setiawan |
| Date Deposited: | 18 Feb 2022 01:19 |
| Last Modified: | 18 Feb 2022 01:19 |
| URI: | http://repository.lppm.unila.ac.id/id/eprint/39465 |
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