Citromycin Isolated from the Antarctic Marine-Derived Fungi, Sporothrix sp., Inhibits Ovarian Cancer Cell Invasion via Suppression of ERK Signaling

• Published in: Marine drugs Vol. 20; no. 5; p. 275
• Main Authors: Choi, He Yun, Ahn, Ji-Hye, Kwon, Haeun, Yim, Joung Han, Lee, Dongho, Choi, Jung-Hye
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 20.04.2022; MDPI
• Subjects: Antibiotics; Antimicrobial agents; Antitumor agents; Biological activity; Cancer; Cancer therapies; Cell adhesion & migration; Cell migration; Cells; Chemotherapy; citromycin; Cytotoxicity; Ectopic expression; ERK1/2 pathway; Extracellular; Extracellular signal-regulated kinase; Fungi; Gelatinase A; Gelatinase B; Gene expression; invasion; Invasiveness; Kinases; Liver cancer; Marine environment; Markers; Matrix metalloproteinase; Matrix metalloproteinases; Mesenchyme; Metabolites; Metalloproteinase; Metastasis; Microorganisms; MMP2 and MMP9; Ovarian cancer; Ovaries; Polar environments; Signaling; Sporothrix; Sporothrix sp; MMP2 and MMP9; citromycin; Sporothrix sp; ERK1/2 pathway; invasion; ovarian cancer
• ISSN: 1660-3397; 1660-3397
• DOI: 10.3390/md20050275

Recently, microorganisms and their metabolites in the Antarctic marine environment have attracted attention as useful sources for novel therapeutics, including anticancer drugs. Here, we investigated the effects of citromycin, isolated from the Antarctic marine-derived fungus, sp., on human ovarian cancer cells. Citromycin inhibited the migration and invasion of human ovarian cancer SKOV3 and A2780 cells, but had no cytotoxic activity against them. Additionally, it inhibited the expression of epithelial-mesenchymal transition (EMT) markers and the activation of matrix metalloproteinase (MMP)-2 and MMP9. Moreover, extracellular signal-regulated kinase (ERK)-1/2 signaling was inhibited after citromycin treatment, and the ectopic expression of ERK negated the anti-invasive activity of citromycin. Our findings suggest that citromycin inhibits the migration and invasion of human ovarian cancer cells by downregulating the expression levels of EMT markers and MMP-2/9 via inhibition of the ERK1/2 pathway.