Transcriptomic analysis of marine endophytic fungi extract identifies highly enriched anti-fungal fractions targeting cancer pathways in HepG2 cell lines

Background: Marine endophytic fungi (MEF) are good sources of structurally unique and biologically active secondary metabolites. Due to the increase in antimicrobial resistance, the secondary metabolites from MEF ought to be fully explored to identify candidates which could serve as lead compounds for novel drug development. These secondary metabolites might also be useful for development of new cancer drugs. In this study, ethyl acetate extracts from marine endophytic fungal cultures were tested for their antifungal activity and anticancer properties against C. albicans and the human liver cancer cell line HepG2, respectively. The highly enriched fractions were also analyzed by high performance liquid chromatography coupled with high resolution mass spectrometry (HPLC-HRMS) and their effect on the HepG2 cells was assessed via transcriptomics and with a proliferation assay. Results: We demonstrated that the fractions could reduce proliferation in HepG2 cells. The detailed transcriptome analysis revealed regulation of several cancer-and metabolism-related pathways and gene ontologies. The down-regulated pathways included, cell cycle, p53 signaling, DNA replication, sphingolipid metabolism and drug metabolism by cytochrome P450. The upregulated pathways included HIF-1 signaling, focal adhesion, necroptosis and transcriptional mis-regulation of cancer. Furthermore, a protein interaction network was constructed based on the 26 proteins distinguishing the three treatment conditions from the untreated cells. This network was composed of central functional components associated with metabolism and cancer such as TNF, MAPK, TRIM21 and one component contained APP. Conclusions: The purified fractions from MEF investigated in this study showed antifungal activity against C. albicans and S. cerevisiae alone or both and reduced proliferation of the human liver cancer cell line HepG2 implicating regulation of several cancer-and metabolism-related pathways. The data from this study could be instrumental in identifying new pathways associated with liver cancer anti-proliferative processes which can be used for the development of novel antifungal and anti-cancer drugs.