Taiwan cobra cardiotoxin III suppresses EGF/EGFR-mediated epithelial-to-mesenchymal transition and invasion of human breast cancer MDA-MB-231 cells

Toxicon : Official Journal of the International Society on Toxinology
Pei-Chien TsaiShinne-Ren Lin

Abstract

Breast cancer is a highly malignant carcinoma and most deaths of breast cancer are caused by metastasis. The epithelial-to-mesenchymal transition (EMT) has emerged as a pivotal event in the development of the invasive and metastatic potentials of cancer progression. Epidermal growth factor (EGF) and its receptor, EGFR, play roles in cancer metastasis. CTX III, a basic polypeptide isolated from Naja naja atra venom, has been shown to exhibit anticancer activity; however, the effect of CTX III on the EMT of cancer cells remains elusive. CTX III treatment resulted in morphological changes from elongated and spindle shape to rounded and epithelial-like shape, induced upregulation of E-cadherin and concurrent downregulation of N-cadherin and Vimentin protein levels, corresponding to observed decreases in cell migration and invasion. CTX III treatment also decreased the expression of Snail and Twist in EGF-induced MDA-MB-231 cells. Concurrently, CTX III efficiently inhibited the EGFR phosphorylation and downstream activation of phosphatidylinositol 3-kinase (PI3K)/Akt and ERK1/2. The EGFR specific inhibitor AG1478 significantly suppressed ERK1/2 and Akt phosphorylation, cell migration and invasion, as well as the expressional changes...Continue Reading

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Citations

May 3, 2016·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Tong GaoLian-Hong Li
Dec 1, 2017·Toxins·Félix A Urra, Ramiro Araya-Maturana
Mar 3, 2018·Toxins·Shu-Zhi Wang, Zheng-Hong Qin
May 20, 2020·Seminars in Cancer Biology·Félix A Urra, Ramiro Araya-Maturana
Dec 5, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Sepideh MirzaeiManoj Garg
Jul 20, 2020·Toxicon : Official Journal of the International Society on Toxinology·Danielle McCulloughCarol M Trim

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