Transcriptomic analysis of marine endophytic fungi extract identifies highly enriched anti-fungal fractions targeting cancer pathways in HepG2 cell lines.
Antifungal Agents
/ chemistry
Antineoplastic Agents
/ chemistry
Apoptosis
/ drug effects
Candida albicans
/ drug effects
Cell Proliferation
/ drug effects
Endophytes
/ chemistry
Hep G2 Cells
Humans
Microbial Sensitivity Tests
Protein Interaction Maps
Saccharomyces cerevisiae
/ drug effects
Seaweed
/ chemistry
Transcriptome
/ genetics
Anti-cancer extract
Anti-fungal resistance
Cancer pathways
HepG2
Marine endophytic fungi
Proliferation
Protein interaction network
Seaweed
Journal
BMC genomics
ISSN: 1471-2164
Titre abrégé: BMC Genomics
Pays: England
ID NLM: 100965258
Informations de publication
Date de publication:
30 Mar 2020
30 Mar 2020
Historique:
received:
10
04
2019
accepted:
18
03
2020
entrez:
2
4
2020
pubmed:
2
4
2020
medline:
22
12
2020
Statut:
epublish
Résumé
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. 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. 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.
Sections du résumé
BACKGROUND
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
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
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.
Identifiants
pubmed: 32228434
doi: 10.1186/s12864-020-6684-z
pii: 10.1186/s12864-020-6684-z
pmc: PMC7106652
doi:
Substances chimiques
Antifungal Agents
0
Antineoplastic Agents
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
265Subventions
Organisme : Deutscher Akademischer Austauschdienst
ID : P/12/08960
Organisme : World Bank Group
ID : ACE02-WACCBIP: Awandare
Organisme : World Bank Group
ID : ACE02-WACCBIP: Awandare
Organisme : Wellcome Trust
ID : 107755/Z/15/Z: Awandare
Pays : United Kingdom
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