An Amiloride Derivative Capable Of Inducing Er Stress And Cell Death In Highly Invasive Breast Cancer

Metastasis, which is the spread of tumors from their place of origin to other locations in the body via the lymph or blood, is associated with a significant increase in morbidity and mortality. Studies on amiloride, an FDA-approved diuretic, have shown it to suppress metastatic characteristics such as cell invasion and suppression, and impair their proliferation and viability. Here we show that 38B, a cell-permeant amiloride derivative, is more efficacious at causing cell death of cancer cells than amiloride. We also show that the cell death produced by 38B does not seem to be caused by apoptosis, autophagy, or calcium-dependent necrosis. However, bright field and immunofluorescence microscopy reveal vacuole formation and ER stress in cells, characteristics typically associated with a recently discovered type of cell death known as paraptosis. Since cancer cells have shown to be efficient at evading common forms of cell death such as apoptosis, the discovery of alternative pathways of cell death and a good understanding of the drugs that activate them can be can be key in the improvement of cancer therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5489. doi:10.1158/1538-7445.AM2011-5489