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

Yusuke Hanaki, Nichika Iwase, Yasunori Sugiyama, Sena Miyoshi, Ryo C. Yanagita
In: BPB Reports · 2023 · vol. 6(3) , pp. 103–107 · doi:10.1248/bpbreports.6.3_103 · W4380537154
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⚙ AI-generated summary by claude@2026-06, 2026-06-13 ⓘ

Vitetrifolin D from *Vitex rotundifolia* was identified as an inhibitor of phorbol ester–induced E-cadherin downregulation in HHUA endometrial cells, though it exhibits some cytotoxicity.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-13 · read from full text ⓘ

The paper studied whether small-molecule inhibitors could block TPA-induced epithelial–mesenchymal transition–related morphological changes and E-cadherin loss in HHUA endometrial cells grown on collagen type I gels, building on prior work showing that the PKC activator 12-O-tetradecanoylphorbol 13-acetate (TPA) causes spheroids to transform into scattered spindle cells. Using a cell morphology-based screening approach, the authors isolated vitetrifolin D from Vitex rotundifolia leaves and found it suppressed the TPA-induced downregulation of E-cadherin, an adherens junction protein. The major limitation explicitly stated is that vitetrifolin D showed modest cytotoxicity at the concentration needed to inhibit E-cadherin downregulation, making it unsuitable as a drug for endometrial disorders. This paper is centrally about endometriosis — it explicitly links EMT in endometrial cells to the development of endometriosis and demonstrates an inhibitor of TPA-driven junction loss relevant to that EMT process.

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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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Report 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 2023 Volume 6 Issue 3 Pages 103-107 Details 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. © 2023 The Pharmaceutical Society of Japan BPB Reports applies the Creative Commons Attribution (CCBY) license to works we published. The license was developed to facilitate open access - namely, free immediate access to, and unrestricted reuse of, original works to all types. Under this license, authors agree to make articles legally available for reuse, without permissions of fees, for virtually any purpose. Anyone may copy, distribute, or reuse these articles, as long as the author and original source are properly cited. https://creativecommons.org/licenses/by/4.0/ Favorites & Alerts Recently viewed articles

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