Pyrrolidinium-type fullerene derivative-induced apoptosis by the generation of reactive oxygen species in HL-60 cells.
The biological activities of C(60)-bis(N,N-dimethylpyrrolidinium iodide), a water-soluble cationic fullerene derivative, on human promyeloleukaemia (HL-60) cells were investigated. The pyrrolidinium fullerene derivative showed cytotoxicity in HL-60 cells. The characteristics of apoptosis, such as DNA fragmentation and condensation of chromatin in HL-60 cells, were observed by exposure to the pyrrolidinium fullerene derivative. Caspase-3 and -8 were activated and cytochrome c was also released from mitochondria. The generation of reactive oxygen species (ROS) by the pyrrolidinium fullerene derivative was observed by DCFH-DA, a fluorescence probe for the detection of ROS. Pre-treatment with alpha-tocopherol suppressed cell death and intracellular oxidative stress caused by the pyrrolidinium fullerene derivative. The apoptotic cell death induced by the pyrrolidinium fullerene derivative was suggested to be mediated by ROS generated by the pyrrolidinium fullerene derivative.
Nishizawa
Chiho
C
Department of Pharmaceutical Sciences, Faculty of Pharmacy, Keio University, Tokyo, Japan.
Hashimoto
Noriyuki
N
Yokoo
Sachiko
S
Funakoshi-Tago
Megumi
M
Kasahara
Tadashi
T
Takahashi
Kyoko
K
Nakamura
Shigeo
S
Mashino
Tadahiko
T
D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D037741:Fullerenes / Q000737:chemistry / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D015394:Molecular Structure; D011759:Pyrrolidines / Q000737:chemistry / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*
C547107:C60-bis(N,N-dimethylpyrrolidinium); D037741:Fullerenes; D011759:Pyrrolidines; D017382:Reactive Oxygen Species; D045304:Cytochromes c; D053148:Caspase 3; D053181:Caspase 8