Simultaneous mitochondrial Ca(2+) overload and proteasomal inhibition are responsible for the induction of paraptosis in malignant breast cancer cells

Mi Jin Yoon; Eun Hee Kim; Taeg Kyu Kwon; Sun Ah Park; Kyeong Sook Choi

doi:10.1016/j.canlet.2012.05.018

Simultaneous mitochondrial Ca(2+) overload and proteasomal inhibition are responsible for the induction of paraptosis in malignant breast cancer cells

Cancer Lett. 2012 Nov 28;324(2):197-209. doi: 10.1016/j.canlet.2012.05.018. Epub 2012 May 22.

Authors

Mi Jin Yoon¹, Eun Hee Kim, Taeg Kyu Kwon, Sun Ah Park, Kyeong Sook Choi

Affiliation

¹ Department of Molecular Science & Technology, Institute for Medical Sciences, Ajou University School of Medicine, Suwon 443-749, Republic of Korea.

PMID: 22634500
DOI: 10.1016/j.canlet.2012.05.018

Abstract

In this study, we investigated the role of Ca(2+) in curcumin-induced paraptosis, a cell death mode that is accompanied by dilation of mitochondria and the endoplasmic reticulum (ER). Curcumin induced mitochondrial Ca(2+) 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(+)/Ca(2+) exchanger (mNCX) and proteasomes can trigger a sustained mitochondrial Ca(2+) overload and effectively induce paraptosis in malignant breast cancer cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents, Phytogenic / pharmacology*
Antineoplastic Combined Chemotherapy Protocols / pharmacology
Boronic Acids / pharmacology
Bortezomib
Breast Neoplasms / enzymology
Breast Neoplasms / pathology*
Calcium / metabolism*
Cell Death / drug effects
Cell Line, Tumor
Clonazepam / analogs & derivatives
Clonazepam / pharmacology
Curcumin / pharmacology*
Dose-Response Relationship, Drug
Endoplasmic Reticulum / drug effects
Endoplasmic Reticulum / metabolism
Endoplasmic Reticulum / pathology
Female
Humans
Mitochondria / drug effects*
Mitochondria / metabolism
Mitochondria / pathology
Protease Inhibitors / pharmacology*
Proteasome Endopeptidase Complex / metabolism
Proteasome Inhibitors*
Pyrazines / pharmacology
Sodium-Calcium Exchanger / antagonists & inhibitors
Sodium-Calcium Exchanger / metabolism
Thiazepines / pharmacology
Time Factors

Substances

Antineoplastic Agents, Phytogenic
Boronic Acids
Protease Inhibitors
Proteasome Inhibitors
Pyrazines
Sodium-Calcium Exchanger
Thiazepines
Clonazepam
Bortezomib
CGP 37157
Proteasome Endopeptidase Complex
Curcumin
Calcium