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

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 associated with EMT markers in EGF-induced MDA-MB-231 cells. CTX III inhibitory effect on EGF-evoked invasion of MDA-MB-231 cells is mediated through suppressing EGF/EGFR activation and EMT process.

• Authors: Pei-Chien Tsai, Yaw-Syan Fu, Long-Sen Chang, Shinne-Ren Lin
• Journal: Toxicon : official journal of the International Society on Toxinology (Toxicon) Vol. 111 Pg. 108-20 (Mar 01 2016) ISSN: 1879-3150 [Electronic] England
• PMID: 26774845 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier Ltd. All rights reserved.

Chemical References

• Biomarkers, Tumor
• Cobra Cardiotoxin Proteins
• cardiotoxin III, Naja naja atra
• Epidermal Growth Factor
• Phosphatidylinositol 3-Kinases
• ErbB Receptors
• Proto-Oncogene Proteins c-akt
• Extracellular Signal-Regulated MAP Kinases
• Matrix Metalloproteinase 9

Topics

• Biomarkers, Tumor
• Breast Neoplasms (metabolism, pathology)
• Cell Line, Tumor
• Cobra Cardiotoxin Proteins (pharmacology)
• Epidermal Growth Factor (metabolism)
• Epithelial-Mesenchymal Transition (drug effects)
• ErbB Receptors (metabolism)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Female
• Humans
• Matrix Metalloproteinase 9 (genetics, metabolism)
• Neoplasm Invasiveness
• Phosphatidylinositol 3-Kinases (genetics, metabolism)
• Proto-Oncogene Proteins c-akt (genetics, metabolism)