Cyclic pentapeptide compounds have garnered much attention as a drug discovery resource. This study focused on the characterization and anti-benign prostatic hyperplasia (BPH) properties of avellanin A from Aspergillus fumigatus fungus in marine sediment samples collected in the Beibu Gulf of Guangxi Province in China. The antiproliferative effect and molecular mechanism of avellanin A were explored in testosterone propionate (TP)-induced RWPE-1 cells. The transcriptome results showed that avellanin A significantly blocked the ECM–receptor interaction and suppressed the downstream PI3K-Akt signalling pathway. Molecular docking revealed that avellanin A has a good affinity for the cathepsin L protein, which is involved in the terminal degradation of extracellular matrix components. Subsequently, qRT-PCR analysis revealed that the expression of the genes COL1A1, COL1A2, COL5A2, COL6A3, MMP2, MMP9, ITGA2, and ITGB3 was significantly downregulated after avellanin A intervention. The Western blot results also confirmed that it not only reduced ITGB3 and FAK/p-FAK protein expression but also inhibited PI3K/p-PI3K and Akt/p-Akt protein expression in the PI3K-Akt signalling pathway. Furthermore, avellanin A downregulated Cyclin D1 protein expression and upregulated Bax, p21^WAF1/Cip1, and p53 proapoptotic protein expression in TP-induced RWPE-1 cells, leading to cell cycle arrest and inhibition of cell proliferation. The results of this study support the use of avellanin A as a potential new drug for the treatment of BPH.

The discovery of novel marine natural products and their sustainable application continue to be vital focuses in marine biological research. The aim of this study is to investigate the inhibitory effect of the compound 5Z-7-Oxozeaenol isolated from the fungus Curvularia sp. MDCW-1060 on the proliferation of MDA-MB-231 cells and its molecular mechanism. A series of functional assays, including 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, Transwell migration, and colony formation, were employed to evaluate the effects of 5Z-7-Oxozeaenol on cellular viability, apoptosis, migration, and clonogenicity. The RNA sequencing (RNA-seq) coupled with bioinformatic analysis was conducted to identify affected differentiated gene expression and signaling pathways. The molecular docking was performed to predict potential protein targets, and Western blot was used to validate expression and phosphorylation levels of key signaling molecules. The results demonstrated that 5Z-7-Oxozeaenol significantly suppressed proliferation and migration while promoting apoptosis in MDA-MB-231 cells. The transcriptomic analysis indicated enrichment in pathways related to cancer, cytokine–cytokine receptor interaction, MAPK and PI3K-Akt signaling, and cell adhesion molecules. The molecular docking suggested a high binding affinity between 5Z-7-Oxozeaenol and PTPRN. While Western blot analysis confirmed the downregulation of phosphorylated FAK, PI3K, Akt, and MAPK, along with reduced cyclin D1 expression. Additionally, 5Z-7-Oxozeaenol upregulated the pro-apoptotic proteins p53 and cleaved caspase-3. In conclusion, 5Z-7-Oxozeaenol exerts potent antitumor effects on MDA-MB-231 cells through multi-pathway inhibition and induction of apoptosis, highlighting its potential as a marine-derived therapeutic candidate for breast cancer treatment.