| RRC ID |
41806
|
| Author |
Simamura E, Hirai K, Shimada H, Pan J, Koyama J.
|
| Title |
Mitochondrial damage prior to apoptosis in furanonaphthoquinone treated lung cancer cells.
|
| Journal |
Cancer Detect Prev
|
| Abstract |
The mechanisms of the antitumor reactions of 2-methylnaphtho[2,3-b]furan-4,9-dione (FNQ3) to human lung adenocarcinoma A549 cells were investigated. A549 cells that received 1.25 microg/ml FNQ3 (IC(50) at 0.35 microg/ml) developed intensive mitochondrial H(2)O(2) production at 1 h. Selective structural mitochondrial swelling, alteration of mitochondrial membrane potential, and cytochrome c and caspase-9 release from the mitochondria occurred 18-24 h later. alpha-Tocopherol inhibited the alteration of both mitochondrial permeability and the leakage of procaspase-9. The caspase-9 was then activated in the cytosol. The expression of Bcl-2 oncoprotein was suppressed by FNQ3, and resulted in apoptosis. The higher dose of 5 microg/ml induced necrosis via severe mitochondrial breakage. These results showed that FNQ3 targets the mitochondria of A549 cells to produce a reactive oxygen species resulting in apoptosis and necrosis.
|
| Volume |
27(1)
|
| Pages |
5-13
|
| Published |
2003-1-1
|
| DOI |
10.1016/s0361-090x(02)00174-5
|
| PII |
S0361090X02001745
|
| PMID |
12600411
|
| MeSH |
Adenocarcinoma / metabolism
Adenocarcinoma / pathology
Adenocarcinoma / ultrastructure
Antineoplastic Agents, Phytogenic / pharmacology*
Antioxidants / pharmacology
Apoptosis / drug effects*
Blotting, Western
Caspase 9
Caspases / metabolism
Cytochrome c Group / metabolism
Cytoplasm / chemistry
DNA Fragmentation
Dose-Response Relationship, Drug
Electrophoresis, Polyacrylamide Gel
Flow Cytometry
Genes, bcl-2 / drug effects
Humans
Hydrogen Peroxide / metabolism
Lung Neoplasms / metabolism
Lung Neoplasms / pathology
Lung Neoplasms / ultrastructure
Membrane Potentials / drug effects
Microscopy, Confocal
Microscopy, Electron
Mitochondria / drug effects
Mitochondria / pathology*
Mitochondria / ultrastructure
Naphthoquinones / pharmacology*
Necrosis
Permeability / drug effects
Tumor Cells, Cultured
alpha-Tocopherol / pharmacology
|
| Times Cited |
15
|
|
WOS Category
|
ONCOLOGY
|
| Resource |
| Human and Animal Cells |
A549(RCB0098) |
