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Citromycin Isolated from the Antarctic Marine-Derived Fungi,Sporothrix sp., Inhibits Ovarian Cancer Cell Invasion via Suppression of ERK Signaling
Authors:He Yun Choi  Ji-Hye Ahn  Haeun Kwon  Joung Han Yim  Dongho Lee  Jung-Hye Choi
Affiliation:1.Department of Biomedical and Pharmaceutical Sciences, Kyung Hee University, Seoul 02447, Korea;2.Department of Oriental Pharmacy, Woosuk University, Jeonju 55338, Korea;3.Department of Plant Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Korea; (H.K.); (D.L.);4.Korea Polar Research Institute, Korea Ocean Research and Development Institute, Incheon 21990, Korea;5.College of Pharmacy, Kyung Hee University, Seoul 02447, Korea
Abstract: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, Sporothrix 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.
Keywords:citromycin   Sporothrix sp.   ovarian cancer   invasion   MMP2 and MMP9   ERK1/2 pathway
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