Inhibition of mitochondrial respiration mediates apoptosis induced by the anti-tumoral alkaloid lamellarin D
被引:96
作者:
Ballot, Caroline
论文数: 0引用数: 0
h-index: 0
机构:
Univ Lille 2, INSERM, U837, F-59045 Lille, France
Univ Lille 2, Fac Med, F-59045 Lille, FranceUniv Lille 2, INSERM, U837, F-59045 Lille, France
Ballot, Caroline
[1
,2
]
Kluza, Jerome
论文数: 0引用数: 0
h-index: 0
机构:
Univ Lille 2, INSERM, U837, F-59045 Lille, France
Univ Lille 2, Fac Med, F-59045 Lille, FranceUniv Lille 2, INSERM, U837, F-59045 Lille, France
Kluza, Jerome
[1
,2
]
Lancel, Steve
论文数: 0引用数: 0
h-index: 0
机构:
Univ Lille 2, Fac Med, EA 2689, F-59045 Lille, FranceUniv Lille 2, INSERM, U837, F-59045 Lille, France
Lancel, Steve
[5
]
Martoriati, Alain
论文数: 0引用数: 0
h-index: 0
机构:
Univ Lille 2, INSERM, U837, F-59045 Lille, France
Univ Lille 2, Fac Med, F-59045 Lille, FranceUniv Lille 2, INSERM, U837, F-59045 Lille, France
Martoriati, Alain
[1
,2
]
Hassoun, Sidi Mohamed
论文数: 0引用数: 0
h-index: 0
机构:
Univ Lille 2, Fac Med, EA 2689, F-59045 Lille, FranceUniv Lille 2, INSERM, U837, F-59045 Lille, France
Hassoun, Sidi Mohamed
[5
]
Mortier, Laurent
论文数: 0引用数: 0
h-index: 0
机构:
Univ Lille 2, INSERM, U837, F-59045 Lille, France
Univ Lille 2, Fac Med, F-59045 Lille, FranceUniv Lille 2, INSERM, U837, F-59045 Lille, France
Mortier, Laurent
[1
,2
]
Vienne, Jean-Claude
论文数: 0引用数: 0
h-index: 0
机构:
CHRU, Ctr Biol Pathol, Lille, FranceUniv Lille 2, INSERM, U837, F-59045 Lille, France
Vienne, Jean-Claude
[3
]
Briand, Gilbert
论文数: 0引用数: 0
h-index: 0
机构:
CHRU, Ctr Biol Pathol, Lille, FranceUniv Lille 2, INSERM, U837, F-59045 Lille, France
Briand, Gilbert
[3
]
Formstecher, Pierre
论文数: 0引用数: 0
h-index: 0
机构:
Univ Lille 2, INSERM, U837, F-59045 Lille, France
Univ Lille 2, Fac Med, F-59045 Lille, FranceUniv Lille 2, INSERM, U837, F-59045 Lille, France
Formstecher, Pierre
[1
,2
]
论文数: 引用数:
h-index:
机构:
Bailly, Christian
[1
,2
]
Neviere, Remi
论文数: 0引用数: 0
h-index: 0
机构:
Univ Lille 2, Fac Med, EA 2689, F-59045 Lille, FranceUniv Lille 2, INSERM, U837, F-59045 Lille, France
Neviere, Remi
[5
]
Marchetti, Philippe
论文数: 0引用数: 0
h-index: 0
机构:
Univ Lille 2, INSERM, U837, F-59045 Lille, France
Univ Lille 2, Fac Med, F-59045 Lille, France
CHRU, Ctr Biol Pathol & Banque Tissus, Lille, FranceUniv Lille 2, INSERM, U837, F-59045 Lille, France
Marchetti, Philippe
[1
,2
,4
]
机构:
[1] Univ Lille 2, INSERM, U837, F-59045 Lille, France
[2] Univ Lille 2, Fac Med, F-59045 Lille, France
[3] CHRU, Ctr Biol Pathol, Lille, France
[4] CHRU, Ctr Biol Pathol & Banque Tissus, Lille, France
[5] Univ Lille 2, Fac Med, EA 2689, F-59045 Lille, France
Lamellarin D (Lam D), a marine alkaloid, exhibits a potent cytotoxicity against many different tumors. The pro-apoptotic function of Lam D has been attributed to its direct induction of mitochondrial permeability transition (MPT). This study was undertaken to explore the mechanisms through which Lam D promotes changes in mitochondrial function and as a result apoptosis. The use of eight Lam derivatives provides useful structure-apoptosis relationships. We demonstrate that Lam D and structural analogues induce apoptosis of cancer cells by acting directly on mitochondria inducing reduction of mitochondrial membrane potential, swelling and cytochrome c release. Cyclosporin A, a well-known inhibitor of MPT, completely prevents mitochondrial signs of apoptosis. The drug decreases calcium uptake by mitochondria but not by microsomes indicating that Lam D-dependent permeability is specific to mitochondrial membranes. In addition, upon Lam D exposure, a rapid decline of mitochondrial respiration and ATP synthesis occurs in isolated mitochondria as well as in intact cells. Evaluation of the site of action of Lam D on the electron-transport chain revealed that the activity of respiratory chain complex III is reduced by a half. To determine whether Lam D could induce MPT-dependent apoptosis by inhibiting mitochondrial respiration, we generated respiration-deficient cells (rho 0) derived from human melanoma cells. In comparison to parental cells, rho 0 cells are totally resistant to the induction of MPT-dependent apoptosis by Lam D. Our results indicate that functional mitochondria are required for Lam D-induced apoptosis. Inhibition of mitochondrial respiration is responsible for MPT-dependent apoptosis of cancer cells induced by Lam-D.
机构:
Univ Lille 2, Fac Med, INSERM, Jean Pierre Aubert Res Ctr,U837, F-59045 Lille, FranceUniv Lille 2, Fac Med, INSERM, Jean Pierre Aubert Res Ctr,U837, F-59045 Lille, France
Gallego, M-A
Ballot, C.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Lille 2, Fac Med, INSERM, Jean Pierre Aubert Res Ctr,U837, F-59045 Lille, FranceUniv Lille 2, Fac Med, INSERM, Jean Pierre Aubert Res Ctr,U837, F-59045 Lille, France
Ballot, C.
Kluza, J.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Lille 2, Fac Med, INSERM, Jean Pierre Aubert Res Ctr,U837, F-59045 Lille, FranceUniv Lille 2, Fac Med, INSERM, Jean Pierre Aubert Res Ctr,U837, F-59045 Lille, France
Kluza, J.
Hajji, N.
论文数: 0引用数: 0
h-index: 0
机构:
Karolinska Inst, Inst Environm Med, S-10401 Stockholm, SwedenUniv Lille 2, Fac Med, INSERM, Jean Pierre Aubert Res Ctr,U837, F-59045 Lille, France
Hajji, N.
Martoriati, A.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Lille 2, Fac Med, INSERM, Jean Pierre Aubert Res Ctr,U837, F-59045 Lille, FranceUniv Lille 2, Fac Med, INSERM, Jean Pierre Aubert Res Ctr,U837, F-59045 Lille, France
Martoriati, A.
Castera, L.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Lille 2, Fac Med, INSERM, Jean Pierre Aubert Res Ctr,U837, F-59045 Lille, FranceUniv Lille 2, Fac Med, INSERM, Jean Pierre Aubert Res Ctr,U837, F-59045 Lille, France
Castera, L.
Cuevas, C.
论文数: 0引用数: 0
h-index: 0
机构:
PharmaMar, E-28770 Madrid, SpainUniv Lille 2, Fac Med, INSERM, Jean Pierre Aubert Res Ctr,U837, F-59045 Lille, France
Cuevas, C.
Formstecher, P.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Lille 2, Fac Med, INSERM, Jean Pierre Aubert Res Ctr,U837, F-59045 Lille, FranceUniv Lille 2, Fac Med, INSERM, Jean Pierre Aubert Res Ctr,U837, F-59045 Lille, France
Formstecher, P.
Joseph, B.
论文数: 0引用数: 0
h-index: 0
机构:
Karolinska Inst, Inst Environm Med, S-10401 Stockholm, SwedenUniv Lille 2, Fac Med, INSERM, Jean Pierre Aubert Res Ctr,U837, F-59045 Lille, France
Joseph, B.
Kroemer, G.
论文数: 0引用数: 0
h-index: 0
机构:
Inst Gustave Roussy, INSERM, U848, F-94805 Villejuif, FranceUniv Lille 2, Fac Med, INSERM, Jean Pierre Aubert Res Ctr,U837, F-59045 Lille, France
Kroemer, G.
Bailly, C.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Lille 2, Fac Med, INSERM, Jean Pierre Aubert Res Ctr,U837, F-59045 Lille, FranceUniv Lille 2, Fac Med, INSERM, Jean Pierre Aubert Res Ctr,U837, F-59045 Lille, France
Bailly, C.
Marchetti, P.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Lille 2, Fac Med, INSERM, Jean Pierre Aubert Res Ctr,U837, F-59045 Lille, FranceUniv Lille 2, Fac Med, INSERM, Jean Pierre Aubert Res Ctr,U837, F-59045 Lille, France
机构:
Univ Lille 2, Fac Med, INSERM, Jean Pierre Aubert Res Ctr,U837, F-59045 Lille, FranceUniv Lille 2, Fac Med, INSERM, Jean Pierre Aubert Res Ctr,U837, F-59045 Lille, France
Gallego, M-A
Ballot, C.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Lille 2, Fac Med, INSERM, Jean Pierre Aubert Res Ctr,U837, F-59045 Lille, FranceUniv Lille 2, Fac Med, INSERM, Jean Pierre Aubert Res Ctr,U837, F-59045 Lille, France
Ballot, C.
Kluza, J.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Lille 2, Fac Med, INSERM, Jean Pierre Aubert Res Ctr,U837, F-59045 Lille, FranceUniv Lille 2, Fac Med, INSERM, Jean Pierre Aubert Res Ctr,U837, F-59045 Lille, France
Kluza, J.
Hajji, N.
论文数: 0引用数: 0
h-index: 0
机构:
Karolinska Inst, Inst Environm Med, S-10401 Stockholm, SwedenUniv Lille 2, Fac Med, INSERM, Jean Pierre Aubert Res Ctr,U837, F-59045 Lille, France
Hajji, N.
Martoriati, A.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Lille 2, Fac Med, INSERM, Jean Pierre Aubert Res Ctr,U837, F-59045 Lille, FranceUniv Lille 2, Fac Med, INSERM, Jean Pierre Aubert Res Ctr,U837, F-59045 Lille, France
Martoriati, A.
Castera, L.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Lille 2, Fac Med, INSERM, Jean Pierre Aubert Res Ctr,U837, F-59045 Lille, FranceUniv Lille 2, Fac Med, INSERM, Jean Pierre Aubert Res Ctr,U837, F-59045 Lille, France
Castera, L.
Cuevas, C.
论文数: 0引用数: 0
h-index: 0
机构:
PharmaMar, E-28770 Madrid, SpainUniv Lille 2, Fac Med, INSERM, Jean Pierre Aubert Res Ctr,U837, F-59045 Lille, France
Cuevas, C.
Formstecher, P.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Lille 2, Fac Med, INSERM, Jean Pierre Aubert Res Ctr,U837, F-59045 Lille, FranceUniv Lille 2, Fac Med, INSERM, Jean Pierre Aubert Res Ctr,U837, F-59045 Lille, France
Formstecher, P.
Joseph, B.
论文数: 0引用数: 0
h-index: 0
机构:
Karolinska Inst, Inst Environm Med, S-10401 Stockholm, SwedenUniv Lille 2, Fac Med, INSERM, Jean Pierre Aubert Res Ctr,U837, F-59045 Lille, France
Joseph, B.
Kroemer, G.
论文数: 0引用数: 0
h-index: 0
机构:
Inst Gustave Roussy, INSERM, U848, F-94805 Villejuif, FranceUniv Lille 2, Fac Med, INSERM, Jean Pierre Aubert Res Ctr,U837, F-59045 Lille, France
Kroemer, G.
Bailly, C.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Lille 2, Fac Med, INSERM, Jean Pierre Aubert Res Ctr,U837, F-59045 Lille, FranceUniv Lille 2, Fac Med, INSERM, Jean Pierre Aubert Res Ctr,U837, F-59045 Lille, France
Bailly, C.
Marchetti, P.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Lille 2, Fac Med, INSERM, Jean Pierre Aubert Res Ctr,U837, F-59045 Lille, FranceUniv Lille 2, Fac Med, INSERM, Jean Pierre Aubert Res Ctr,U837, F-59045 Lille, France