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Updated: Jul 2, 2025
Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
Screening of growth inhibitors for epithelial-mesenchymal transition-induced cells by TGF-β from plant-based sources
Hirotaka Matsuo1, Hitomi Kawakami2, Naoko Anjiki3
1Tsukuba Division of Research Center for Medicinal Plant Resources, National Institutes of Biomedical Innovation, Health and Nutrition, 1-2 Hachimandai, Tsukuba, 305-8043, Japan. matsu-h@nibiohn.go.jp.
Abstract:
Epithelial-mesenchymal transition (EMT) has recently been associated with cancer invasion, metastasis, and resistance. In our previous study, we discovered nanaomycin K, a natural growth inhibitor for EMT-induced Madin Darby canine kidney (MDCK) cells, from the cultured broth of actinomycetes. However, the screening method was undeveloped, because the activity of nanaomycin K was discovered accidentally. In this study, we established a screening method by analyzing the characteristics of nanaomycin K in MDCK cells. Nanaomycin K showed the characteristic growth inhibitory activity on MDCK cells cultured under four conditions: medium containing dimethyl sulfoxide, SB431542, TGF-β, and a mixture of SB431542 and TGF-β. The activity was stronger in TGF-β-treated cells than in DMSO-treated cells. In the mixture of SB431542 and TGF-β-treated cells, the activity of nanaomycin K was suppressed. The anti-cancer agents, mitomycin C, cisplatin, and staurosporine, lacked the characteristics as that of nanaomycin K for these four treatment conditions. Since these four conditions distinguish between the effects of nanaomycin K and other anti-cancer agents in EMT-induced cells, the screening method was established. Among the 13,427 plant extracts tested, Piper betle leaf extract displayed growth inhibitory activity against EMT-induced cells. Through the purification of the extract via bio-guided fractionation, hydroxychavicol was isolated as an active compound. The cytotoxic activity of hydroxychavicol was stronger in EMT-induced MDCK cells than in control cells. However, its cytotoxic activity was suppressed in EMT-inhibited cells. Furthermore, hydroxychavicol exhibited same activity against SAS cells (human squamous cell carcinoma of the tongue). Thus, we have successfully established a screening method for growth inhibitors of EMT-induced cells and have discovered an inhibitor from plant-based sources.
Insights
Researchers developed a new screening method to find cancer growth inhibitors targeting epithelial-mesenchymal transition (EMT). They identified hydroxychavicol from Piper betle as a potent inhibitor, showing promise for cancer therapy.
Area of Science:
- Oncology
- Cell Biology
- Natural Products Chemistry
Background:
- Epithelial-mesenchymal transition (EMT) is linked to cancer progression, invasion, metastasis, and drug resistance.
- A previous study identified nanaomycin K as a natural inhibitor of EMT-induced Madin Darby canine kidney (MDCK) cells.
- The screening method for such inhibitors was previously undeveloped.
Discussion:
- A novel screening method was established by analyzing nanaomycin K's distinct growth inhibitory characteristics in MDCK cells under four specific culture conditions.
- These conditions differentiated nanaomycin K's activity from conventional anti-cancer agents like mitomycin C, cisplatin, and staurosporine.
- The method leverages the differential activity of inhibitors in TGF-β-stimulated versus unstimulated cells.
Key Insights:
- Hydroxychavicol, isolated from Piper betle leaf extract, demonstrated potent cytotoxic activity against EMT-induced MDCK cells and SAS cancer cells.
- The activity of hydroxychavicol was significantly stronger in EMT-induced cells compared to control cells and was suppressed in EMT-inhibited cells.
- This study successfully established a reliable screening platform for identifying EMT-specific growth inhibitors from natural sources.
Outlook:
- The established screening method provides a robust tool for discovering novel anti-cancer agents targeting EMT.
- Hydroxychavicol represents a promising lead compound for developing new therapeutic strategies against cancers characterized by EMT.
- Further research into hydroxychavicol's mechanism of action and in vivo efficacy is warranted.
