Simultaneous mitochondrial Ca(2+) overload and proteasomal inhibition are responsible for the induction of paraptosis in malignant breast cancer cells.
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.
Department of Molecular Science & Technology, Institute for Medical Sciences, Ajou University School of Medicine, Suwon 443-749, Republic of Korea.
Mi Jin
MJ
Yoon
Eun Hee
EH
Kim
Taeg Kyu
TK
Kwon
Sun Ah
SA
Park
Kyeong Sook
KS
Choi
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D001897:Boronic Acids / Q000494:pharmacology; D000069286:Bortezomib; D001943:Breast Neoplasms / Q000201:enzymology / Q000473:pathology*; D002118:Calcium / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002998:Clonazepam / Q000031:analogs & derivatives / Q000494:pharmacology; D003474:Curcumin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011480:Protease Inhibitors / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D011719:Pyrazines / Q000494:pharmacology; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors / Q000378:metabolism; D013841:Thiazepines / Q000494:pharmacology; D013997:Time Factors
D000972:Antineoplastic Agents, Phytogenic; D001897:Boronic Acids; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; D011719:Pyrazines; D019831:Sodium-Calcium Exchanger; D013841:Thiazepines; D002998:Clonazepam; D000069286:Bortezomib; C079032:CGP 37157; D046988:Proteasome Endopeptidase Complex; D003474:Curcumin; D002118:Calcium