1. Screening of growth inhibitors for epithelial-mesenchymal transition-induced cells by TGF-β from plant-based sources identified the active compound hydroxychavicol from Piper bitle.
- Author
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Matsuo H, Kawakami H, Anjiki N, Kawano N, Fuchino H, Kawahara N, and Yoshimatsu K
- Subjects
- Animals, Dogs, Humans, Benzamides pharmacology, Benzamides chemistry, Cell Proliferation drug effects, Dioxoles pharmacology, Dioxoles chemistry, Eugenol pharmacology, Eugenol analogs & derivatives, Growth Inhibitors pharmacology, Growth Inhibitors chemistry, Growth Inhibitors isolation & purification, Madin Darby Canine Kidney Cells, Plant Extracts pharmacology, Plant Extracts chemistry, Epithelial-Mesenchymal Transition drug effects, Transforming Growth Factor beta metabolism, Piper betle chemistry
- 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., (© 2024. The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy.)
- Published
- 2024
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