| RRC ID |
1938
|
| 著者 |
Qian W, Nishikawa M, Haque AM, Hirose M, Mashimo M, Sato E, Inoue M.
|
| タイトル |
Mitochondrial density determines the cellular sensitivity to cisplatin-induced cell death.
|
| ジャーナル |
Am J Physiol Cell Physiol
|
| Abstract |
We studied the relationship between the mitochondrial density in the cells and the cellular sensitivity to the toxicity of cis-diaminedichloroplatinum II (cisplatin), a potent anticancer agent. Biochemical analyses revealed that the density of mitochondria in the intestinal epithelium changed markedly along its entire length. The density was the highest at the duodenum, medium at the jejunum, and the lowest at the ileum. The sensitivity of epithelial cells to cisplatin toxicity was the highest at the duodenum, medium at the jejunum, and the lowest at the ileum as judged from the occurrence of apoptosis. Similar correlation between the cisplatin sensitivity and mitochondrial density was also observed with in vitro experiments, in which intestinal epithelial cells (IEC-6) and their rho0 cells with reduced number of mitochondria were used. The rho0 cells had a strong resistance to cisplatin compared with the control cells. Cisplatin markedly increased mitochondrial generation of reactive oxygen species in IEC-6 but not in rho0 cells. We analyzed the sensitivity of eight cell lines with different density of mitochondria to cisplatin and found the same positive correlation. These observations clearly show that cellular density of mitochondria is the key factor for the determination of the anticancer activity and side effects of cisplatin.
|
| 巻・号 |
289(6)
|
| ページ |
C1466-75
|
| 公開日 |
2005-12-1
|
| DOI |
10.1152/ajpcell.00265.2005
|
| PII |
00265.2005
|
| PMID |
16107504
|
| MeSH |
Animals
Antineoplastic Agents / pharmacology*
Apoptosis*
Cell Survival / drug effects
Cell Survival / physiology
Cells, Cultured
Cisplatin / pharmacology*
Cyclooxygenase 1 / metabolism
Cytochromes c / metabolism
Epithelial Cells / drug effects
Epithelial Cells / metabolism
Epithelial Cells / ultrastructure
Intestinal Mucosa / cytology
Intestinal Mucosa / drug effects
Intestinal Mucosa / metabolism
Intestine, Small / cytology
Intestine, Small / drug effects
Intestine, Small / metabolism
L-Lactate Dehydrogenase / metabolism
Male
Membrane Potentials / drug effects
Membrane Proteins / metabolism
Mitochondria / drug effects*
Mitochondria / physiology
Mitochondrial Membranes / drug effects
Mitochondrial Membranes / physiology
Rats
Rats, Wistar
Reactive Oxygen Species / metabolism
Superoxide Dismutase / metabolism
|
| IF |
3.485
|
| 引用数 |
73
|
|
WOS 分野
|
PHYSIOLOGY
CELL BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
IEC 6(RCB0993) |
