Curcumin-induced melanoma cell death is associated with mitochondrial permeability transition pore (mPTP) opening.

Abstract

Here we studied the role of mitochondrial permeability transition pore (mPTP) opening in curcumin's cytotoxicity in melanoma cells. In cultured WM-115 melanoma cells, curcumin induced mitochondrial membrane potential (MPP) decrease, cyclophilin-D (CyPD)-adenine nucleotide translocator 1 (ANT-1) (two mPTP components) mitochondrial association and cytochrome C release, indicating mPTP opening. The mPTP blocker sanglifehrin A (SfA) and ANT-1 siRNA-depletion dramatically inhibited curcumin-induced cytochrome C release and WM-115 cell death. CyPD is required for curcumin-induced melanoma cell death. The CyPD inhibitor cyclosporin A (CsA) or CyPD siRNA-depletion inhibited curcumin-induced WM-115 cell death and apoptosis, while WM-115 cells with CyPD over-expression were hyper-sensitive to curcumin. Finally, we found that C6 ceramide enhanced curcumin-induced cytotoxicity probably through facilitating mPTP opening, while CsA and SfA as well as CyPD and ANT-1 siRNAs alleviated C6 ceramide's effect on curcumin in WM-115 cells. Together, these results suggest that curcumin-induced melanoma cell death is associated with mPTP opening.

• Authors: Ying Qiu, Teng Yu, Wei Wang, Kun Pan, Dongmei Shi, Hui Sun
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 448 Issue 1 Pg. 15-21 (May 23 2014) ISSN: 1090-2104 [Electronic] United States
• PMID: 24735534 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Adenine Nucleotide Translocator 1
• Cyclophilin D
• Lactones
• Mitochondrial Membrane Transport Proteins
• Mitochondrial Permeability Transition Pore
• SLC25A4 protein, human
• Spiro Compounds
• sanglifehrin A
• Cytochromes c
• Cyclophilins
• Curcumin

Topics

• Adenine Nucleotide Translocator 1 (genetics, pharmacology)
• Cell Death (drug effects)
• Cell Line, Tumor
• Curcumin (pharmacology)
• Cyclophilin D
• Cyclophilins (biosynthesis)
• Cytochromes c (metabolism)
• Humans
• Lactones (pharmacology)
• Melanoma (pathology)
• Mitochondrial Membrane Transport Proteins (drug effects, physiology)
• Mitochondrial Permeability Transition Pore
• Spiro Compounds (pharmacology)