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

Abstract

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 downregulated 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.

Marine Pyrrole Alkaloids

“…Furthermore, the uniqueness of marine life is reflected by the fact that only a small fraction of the 30,000 marine natural products (MNPs) known at present can also be found in terrestrial sources [1]. Additionally, the isolation and investigation of MNPs is a rapidly expanding field of research at the interface of biology and chemistry [2][3][4][5][6][7][8][9][10]. Looking back to 2009, when only 20,000 MNPs were known, an impressive increase of 50% has been achieved in the past 11 years, which highlights the importance of the marine habitat in this context [11].…”

Marine Natural Products: A Potential Source of Anti-hepatocellular Carcinoma Drugs

“…Among these fractions, three (V1, V3, and V5) were tested for their effects on HepG2 cells at different concentrations (5–15% w/v) via the resazurin metabolic assay. Specifically, compared with untreated HepG2 cells, V5 exhibited anti-cancer bioactivity in a dose-dependent manner with approximately 82% to 16% proliferation inhibition, while V1 at a concentration of 10% (w/v), and V3 at a concentration of 7.5% (w/v), showed the strongest inhibitory effects (approximately 84% and 80%, respectively) . Moreover, this marked inhibition of cellular proliferation was induced by upregulating necroptosis, focal adhesion, and hypoxia inducible factor 1 signaling pathways, while downregulating p53 signaling, cell cycle, and DNA replication pathways .…”

“…Specifically, compared with untreated HepG2 cells, V5 exhibited anti-cancer bioactivity in a dose-dependent manner with approximately 82% to 16% proliferation inhibition, while V1 at a concentration of 10% (w/v), and V3 at a concentration of 7.5% (w/v), showed the strongest inhibitory effects (approximately 84% and 80%, respectively). 99 Moreover, this marked inhibition of cellular proliferation was induced by upregulating necroptosis, focal adhesion, and hypoxia inducible factor 1 signaling pathways, while downregulating p53 signaling, cell cycle, and DNA replication pathways. 99 These fungal extracts may represent promising source materials for the development of new anti-cancer agents.…”

“…Marine endophytic fungi (MEF) are also known as good sources of biologically active secondary metabolites. Most recently, Blessie et al 99 tested the biological activity of crude extracts from 143 morphologically distinct seaweed-derived MEFs collected from Ghana beaches. The crude extracts of MEF 134 piqued the authors' interest and were further fractionated by Kupchan fractionation and two rounds of thin layer chromatography, to obtain partially purified fractions.…”

Development of Marine-Derived Compounds for Cancer Therapy

“…The chromomycin SA analogs isolated from marine-derived Streptomyces [113], the cyclic lipoheptapeptides isolated from marine algicolous bacterial [114] and three chromone derivatives isolated from marine-derived Penicillium citrinum [115] were shown to work against lung cancers. The extracts derived from marine sponges [116], alkaloid aaptamine from marine sponges [117] and some extracts from marine fungus [118] decreased the proliferation of liver cancer cells. The salarin C extracted from sponge [119] and yessotoxins (YTXs) produced by marine dinoflagellates [120] were able to kill leukemia cells.…”