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Baicalein inhibits fibronectin-induced epithelial-mesenchymal transition by decreasing activation and upregulation of calpain-2.

ABSTRACT: The extracellular matrix protein fibronectin (FN) facilitates tumorigenesis and the development of breast cancer. Inhibition of the FN-induced cellular response is a potential strategy for breast cancer treatment. In the present study, we investigated the effects of the flavonoid baicalein on FN-induced epithelial-mesenchymal transition (EMT) in MCF-10A breast epithelial cells and in a transgenic mouse MMTV-polyoma middle T antigen breast cancer model (MMTV-PyMT). Baicalein inhibited FN-induced migration, invasion, and F-actin remodeling. Baicalein also suppressed FN-induced downregulation of the epithelial markers E-cadherin and ZO-1 and upregulation of the mesenchymal markers N-cadherin, vimentin, and Snail. Further investigation revealed that calpain-2 was involved in baicalein suppression of FN-induced EMT. Baicalein significantly decreased FN-enhanced calpain-2 expression and activation by suppressing its plasma membrane localization, substrate cleavage, and degradation of its endogenous inhibitor calpastatin. Overexpression of calpain-2 in MCF-10A cells by gene transfection partially blocked the inhibitory effect of baicalein on FN-induced EMT changes. In addition, baicalein inhibited calpain-2 by decreasing FN-increased intracellular calcium ion levels and extracellular signal-regulated protein kinases activation. Baicalein significantly decreased tumor onset, growth, and pulmonary metastasis in a spontaneous breast cancer MMTV-PyMT mouse model. Baicalein also reduced the expression of FN, calpain-2, and vimentin, but increased E-cadherin expression in MMTV-PyMT mouse tumors. Overall, these results revealed that baicalein markedly inhibited FN-induced EMT by inhibiting calpain-2, thus providing novel insights into the pharmacological action and mechanism of baicalein. Baicalein may therefore possess therapeutic potential for the treatment of breast cancer though interfering with extracellular matrix-cancer cell interactions.

SUBMITTER: Chen Y

PROVIDER: S-EPMC6472504 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Baicalein inhibits fibronectin-induced epithelial-mesenchymal transition by decreasing activation and upregulation of calpain-2.

Chen Yan Y Chen Lin L Hong Duanyang D Chen Zongyue Z Zhang Jingyu J Fu Lingyun L Pan Di D Zhang Yanyan Y Xu Yini Y Gan Shiquan S Xiao Chaoda C Tao Ling L Shen Xiangchun X

Cell death & disease 20190418 5

The extracellular matrix protein fibronectin (FN) facilitates tumorigenesis and the development of breast cancer. Inhibition of the FN-induced cellular response is a potential strategy for breast cancer treatment. In the present study, we investigated the effects of the flavonoid baicalein on FN-induced epithelial-mesenchymal transition (EMT) in MCF-10A breast epithelial cells and in a transgenic mouse MMTV-polyoma middle T antigen breast cancer model (MMTV-PyMT). Baicalein inhibited FN-induced ...[more]

PMID: 31000696

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Dataset Information

Baicalein inhibits fibronectin-induced epithelial-mesenchymal transition by decreasing activation and upregulation of calpain-2.

Publications

Baicalein inhibits fibronectin-induced epithelial-mesenchymal transition by decreasing activation and upregulation of calpain-2.

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