PAR1-Mediated Apoptosis and Tumor Regression of Breast Cancer Cells by Vibrio cholerae Hemagglutinin Protease

Recent therapies of cancer have different side effects, so present scenario demands new therapeutic strategies. Bacterial toxins have been reported to show promising results in cancer treatment. Vibrio cholerae hemagglutinin protease (HAP) regresses tumor growth in Swiss albino mice by programmed cell death of mouse breast cancer cells. Treatment with HAP (one µg/week for three successive weeks) reduced solid tumor and enhanced survival of Ehrlich ascites carcinoma (EAC)-induced Swiss albino mice. A good therapeutic agent should specifically kill malignant cells without any effect on the survival of healthy normal cells. HAP induced PAR1 activation in mouse breast cancer cells (EAC). Overexpression of PAR1 has been reported in different malignant cells when compared to normal cells. HAP-induced PAR1 activated the downstream signaling pathways by nuclear translocation of p50-p65 and the phosphorylation of p38 which caused the activation of NFκB and MAP kinase pathways. The NFκB and MAP kinase activation enhanced the cellular ROS levels. The basal ROS level is reported to be higher in malignant cells as compared to normal healthy cells. Malignant cells cross the threshold level of ROS faster than the normal cells and switch on the cascades of cellular apoptosis. HAP-induced PAR1-mediated apoptosis of malignant cells without altering normal healthy cells makes it a good therapeutic agent for cancer treatment.