Abstract
A study on the secondary metabolites of Aspergillus sp. XNM-4, which was derived from marine algae Leathesia nana (Chordariaceae), led to the identification of one previously undescribed (1) and seventeen known compounds (2–18). Their planar structures were established by extensive spectroscopic analyses, while the stereochemical assignments were defined by electronic circular dichroism (ECD) calculations. The biological activities of the compounds were assessed on five human cancer cell lines (PANC-1, A549, MDA-MB-231, Caco-2, and SK-OV-3), and one human normal cell line (HL-7702) using an MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide] assay. Among them, the dimeric naphthopyrones 7, 10 and 12 exhibited potent cytotoxicity. Further mechanism studies showed that 12 induced apoptosis, arrested the cell cycle at the G0/G1 phase in the PANC-1 cells, caused morphological changes and generated ROS; and it induces PANC-1 cells apoptosis via ROS-mediated PI3K/Akt signaling pathway.
Highlights
Marine-derived endophytic fungi have drawn considerable attention for their surprising potential in drug discovery [1,2,3,4,5]
To explore whether the abovementioned reduction in cell viability was caused by the induction the colony numbers decreased to 574 ± 65, 421 ± 30 and 105 ± 21 after treatment with compound 12 of apoptosis, PANC-1 cells were treated with compound 12 (5, 10, and 20 μM) for 72 h
These results showed that compound 12 could inhibit the colony were stained with fluorescein isothiocyanate (Annexin-V FITC) and propidium iodide (PI) and formation of PANC-1 cells
Summary
Marine-derived endophytic fungi have drawn considerable attention for their surprising potential in drug discovery [1,2,3,4,5]. These endophytic fungi can be distributed in every possible marine host, such as plants, invertebrates and vertebrates [6]. In our ongoing efforts to discover the bioactive secondary metabolites of endophytic fungi from the marine brown algae Leathesia nana (Chordariaceae), eighteen compounds were isolated. As the most promising candidate, the cytotoxic mechanism of mechanism of compound 12 in PANC-1 cells was studied preliminarily.
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