Marine fungi, such as species from the Penicillium and Aspergillus genera, are prolific producers of a diversity of natural products with cytotoxic properties. These fungi have been successfully isolated and identified from various marine sources, including sponges, coral, algae, mangroves, sediment, and seawater. The cytotoxic compounds derived from marine fungi can be categorized into five distinct classes: polyketides, peptides, terpenoids and sterols, hybrids, and other miscellaneous compounds. Notably, the pre-eminent group among these compounds comprises polyketides, accounting for 307 out of 642 identified compounds. Particularly, within this collection, 23 out of the 642 compounds exhibit remarkable cytotoxic potency, with IC₅₀ values measured at the nanomolar (nM) or nanogram per milliliter (ng/mL) levels. This review elucidates the originating fungal strains, the sources of isolation, chemical structures, and the noteworthy antitumor activity of the 642 novel natural products isolated from marine fungi. The scope of this review encompasses the period from 1991 to 2023.

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.