Citromycin Isolated from the Antarctic Marine-Derived Fungi, Sporothrix sp., Inhibits Ovarian Cancer Cell Invasion via Suppression of ERK Signaling.
He Yun ChoiJi-Hye AhnHaeun KwonJoung Han YimDongho LeeJung-Hye ChoiPublished in: Marine drugs (2022)
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.
Keyphrases
- epithelial mesenchymal transition
- signaling pathway
- endothelial cells
- poor prognosis
- cell proliferation
- pi k akt
- induced apoptosis
- induced pluripotent stem cells
- small molecule
- binding protein
- cell cycle arrest
- ms ms
- transforming growth factor
- tyrosine kinase
- cell death
- combination therapy
- high resolution
- endoplasmic reticulum stress
- high speed
- protein kinase
- replacement therapy