Cell Morphology-Based Screening Identified Vitetrifolin D from Vitex Rotundifolia as an Inhibitor of Phorbol Ester–Induced Downregulation of E-Cadherin in HHUA Endometrial Cells
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Abstract
The epithelial–mesenchymal transition (EMT) of endometrial cells contributes to the development of endometrial cancer, endometriosis, and adenomyosis. We have recently reported that 12-O-Tetradecanoylphorbol 13-acetate (TPA), a protein kinase C activator, induces EMT in HHUA endometrial cells cultured on collagen type I gels. HHUA cells showed an obvious morphological change from spheroids to scattered spindle cells during the TPA-induced EMT. In this study, we searched for inhibitors of the TPA-induced morphological change, and isolated vitetrifolin D from Vitex rotundifolia leaves. Vitetrifolin D suppressed the TPA-induced downregulation of E-cadherin, a major component of the epithelial adherens junction. Since vitetrifolin D showed a modest cytotoxicity at the concentration required to inhibit E-cadherin downregulation, it would not be suitable as a drug to treat endometrial disorders. However, our cell morphology-based screening could contribute to the discovery of new compounds that inhibit the loss of epithelial cell junctions.
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Cites (3)
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- Corroborating evidence for platelet-induced epithelial-mesenchymal transition and fibroblast-to-myofibroblast transdifferentiation in the development of adenomyosis 2016
- Platelets induce endothelial–mesenchymal transition and subsequent fibrogenesis in endometriosis 2020
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