Nudifloside, a Secoiridoid Glucoside Derived from Callicarpa nudiflora, Inhibits Endothelial-to-Mesenchymal Transition and Angiogenesis in Endothelial Cells by Suppressing Ezrin Phosphorylation

Zhuo, Dongliang; Mei, Yinlong; Lin, Chaozhan; Wu, Aizhi; Luo, Yuehua; Lu, Hong; Fu, Jianjiang

doi:10.7150/jca.91566

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J Cancer 2024; 15(9):2448-2459. doi:10.7150/jca.91566 This issue Cite

Research Paper

Nudifloside, a Secoiridoid Glucoside Derived from Callicarpa nudiflora, Inhibits Endothelial-to-Mesenchymal Transition and Angiogenesis in Endothelial Cells by Suppressing Ezrin Phosphorylation

Dongliang Zhuo¹, Yinlong Mei¹, Chaozhan Lin², Aizhi Wu², Yuehua Luo³, Hong Lu^4✉, Jianjiang Fu^1,5✉

1. School of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang 330004, China.
2. Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
3. Jiangxi Provincial Institute for Drug Control, Nanchang, 330029, China.
4. Network and Educational Technology Center, Jiangxi University of Chinese Medicine, Nanchang 330004, China.
5. Jiangxi Province Key Laboratory for Diagnosis, Treatment, and Rehabilitation of Cancer in Chinese Medicine, China.

Citation:

Zhuo D, Mei Y, Lin C, Wu A, Luo Y, Lu H, Fu J. Nudifloside, a Secoiridoid Glucoside Derived from Callicarpa nudiflora, Inhibits Endothelial-to-Mesenchymal Transition and Angiogenesis in Endothelial Cells by Suppressing Ezrin Phosphorylation. J Cancer 2024; 15(9):2448-2459. doi:10.7150/jca.91566. https://www.jcancer.org/v15p2448.htm

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Abstract

Callicarpa nudiflora is a traditional folk medicine in China used for eliminating stasis to subdue swelling. Several compounds from Callicarpa nudiflora have been proved to show anti-inflammatory, haemostasis, hepatitis, and anti-proliferative effects. Tumor endothelial cells play crucial roles in tumor-induced angiogenesis. Recently, it was demonstrated that ECs may be the important source of cancer associated fibroblasts (CAFs) through endothelial to mesenchymal transition (EndoMT). In this study, we evaluated the effects of nudifloside (NDF), a secoiridoid glucoside from Callicarpa Nudiflora, on TGF-β1-induced EndoMT and VEGF-induced angiogenesis, and the underlying mechanisms were also involved. It was found that NDF significantly inhibited enhanced migration, invasion and F-actin assembly in endothelial cells (ECs) exposed in TGF-β1. NDF obviously reversed expression of several biomarkers associated with EndoMT and recovered the morphological characteristics of ECs and tube-like structure induced by TGF-β1. Furthermore, treatment of NDF resulted in a significant destruction of VEGF-induced angiogenesis in vitro and ex vivo. Data from co-immunoprecipitation assay provided the evidence that Ezrin phosphorylation and the interaction with binding protein can be inhibited by NDF, which can be confirmed by data from Ezrin silencing assay. Collectively, the application of NDF inhibited TGF-β1-induced EndoMT and VEGF-induced angiogenesis in ECs by reducing Ezrin phosphorylation.

Keywords: Nudifloside, EndoMT, angiogenesis, Ezrin, Callicarpa nudiflora.

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APA

Zhuo, D., Mei, Y., Lin, C., Wu, A., Luo, Y., Lu, H., Fu, J. (2024). Nudifloside, a Secoiridoid Glucoside Derived from Callicarpa nudiflora, Inhibits Endothelial-to-Mesenchymal Transition and Angiogenesis in Endothelial Cells by Suppressing Ezrin Phosphorylation. Journal of Cancer, 15(9), 2448-2459. https://doi.org/10.7150/jca.91566.

ACS

Zhuo, D.; Mei, Y.; Lin, C.; Wu, A.; Luo, Y.; Lu, H.; Fu, J. Nudifloside, a Secoiridoid Glucoside Derived from Callicarpa nudiflora, Inhibits Endothelial-to-Mesenchymal Transition and Angiogenesis in Endothelial Cells by Suppressing Ezrin Phosphorylation. J. Cancer 2024, 15 (9), 2448-2459. DOI: 10.7150/jca.91566.

NLM

CSE

Zhuo D, Mei Y, Lin C, Wu A, Luo Y, Lu H, Fu J. 2024. Nudifloside, a Secoiridoid Glucoside Derived from Callicarpa nudiflora, Inhibits Endothelial-to-Mesenchymal Transition and Angiogenesis in Endothelial Cells by Suppressing Ezrin Phosphorylation. J Cancer. 15(9):2448-2459.

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