title: 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.affiliation: Department of Dermatology, Shandong Ji-ning No.1 People's Hospital, Ji-ning City, Shandong Province 272011, PR China. Electronic address: tengyu33@yahoo.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Department of Dermatology, Shandong Ji-ning No.1 People's Hospital, Ji-ning City, Shandong Province 272011, PR China.
authors.forename: Teng
authors.initials: T
authors.lastname: Yu
authors.affiliation: Department of Dermatology, Shandong Ji-ning No.1 People's Hospital, Ji-ning City, Shandong Province 272011, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Dermatology, The Skin Disease Hospital of Ji-ning City, Ji-ning City, Shandong Province 272011, PR China.
authors.forename: Kun
authors.initials: K
authors.lastname: Pan
authors.affiliation: Department of Dermatology, Shandong Ji-ning No.1 People's Hospital, Ji-ning City, Shandong Province 272011, PR China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Shi
authors.affiliation: Department of Dermatology, Shandong Ji-ning No.1 People's Hospital, Ji-ning City, Shandong Province 272011, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Sun
mesh_terms: D033741:Adenine Nucleotide Translocator 1 / Q000235:genetics / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor; D003474:Curcumin / Q000494:pharmacology*; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins / Q000096:biosynthesis; D045304:Cytochromes c / Q000378:metabolism; D006801:Humans; D007783:Lactones / Q000494:pharmacology; D008545:Melanoma / Q000473:pathology*; D033681:Mitochondrial Membrane Transport Proteins / Q000187:drug effects / Q000502:physiology*; D000083162:Mitochondrial Permeability Transition Pore; D013141:Spiro Compounds / Q000494:pharmacology
chemical_list: D033741:Adenine Nucleotide Translocator 1; D000081406:Peptidyl-Prolyl Isomerase F; D007783:Lactones; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; C580832:SLC25A4 protein, human; D013141:Spiro Compounds; C121329:sanglifehrin A; D045304:Cytochromes c; D021983:Cyclophilins; D003474:Curcumin
keywords: Cell death; Curcumin; Cyclophilin-D; Melanoma; Mitochondrial permeability transition pore (mPTP)