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PAR-1 mediated apoptosis of breast cancer cells by V. cholerae hemagglutinin protease

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Abstract

Bacterial toxins have emerged as promising agents in cancer treatment strategy. Hemagglutinin (HAP) protease secreted by Vibrio cholerae induced apoptosis in breast cancer cells and regresses tumor growth in mice model. The success of novel cancer therapies depends on their selectivity for cancer cells with limited toxicity for normal tissues. Increased expression of Protease Activated Receptor-1 (PAR-1) has been reported in different malignant cells. In this study we report that HAP induced activation and over expression of PAR-1 in breast cancer cells (EAC). Immunoprecipitation studies have shown that HAP specifically binds with PAR-1. HAP mediated activation of PAR-1 caused nuclear translocation of p50–p65 and the phosphorylation of p38 which triggered the activation of NFκB and MAP kinase signaling pathways. These signaling pathways enhanced the cellular ROS level in malignant cells that induced the intrinsic pathway of cell apoptosis. PAR-1 mediated apoptosis by HAP of malignant breast cells without effecting normal healthy cells in the same environment makes it a good therapeutic agent for treatment of cancer.

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Acknowledgments

We would like to thank Dr. Rathin Baral (CNCI, India) for providing EAC cells and Dr. Ratna Biswas for her technical suggestion. We are grateful to the central facility of FACS and the technical support of Mr. Somnath Chatterjee for confocal microscopy at Central Facility, NICED, Kolkata. TR is supported by the Post Doctoral Fellowship of Indian Council of Medical Research (ICMR PDF fellowship).

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  1. Division of Pathophysiology, National Institute of Cholera and Enteric Diseases, P-33, CIT Road, Scheme-XM, Beliaghata, Kolkata, 700010, India

    Tanusree Ray & Amit Pal

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Correspondence to Amit Pal.

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Ray, T., Pal, A. PAR-1 mediated apoptosis of breast cancer cells by V. cholerae hemagglutinin protease. Apoptosis 21, 609–620 (2016). https://doi.org/10.1007/s10495-016-1229-2

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