Simultaneous mitochondrial Ca2+ overload and proteasomal inhibition are responsible for the induction of paraptosis in malignant breast cancer cells

In this study, we investigated the role of Ca2+ in curcumin-induced paraptosis, a cell death mode that is accompanied by dilation of mitochondria and the endoplasmic reticulum (ER). Curcumin induced mitochondrial Ca2+ overload selectively in the malignant breast cancer cells, but not in the normal breast cell, contributing to the dilation of mitochondria/ER and subsequent paraptotic cell death. In addition, we found that simultaneous inhibition of the mitochondrial Na+/Ca2+ exchanger (mNCX) and proteasomes can trigger a sustained mitochondrial Ca2+ overload and effectively induce paraptosis in malignant breast cancer cells.