| RRC ID |
39535
|
| 著者 |
Fukumi S, Horiguchi-Yamada J, Nakada S, Nagai M, Ohno T, Yamada H.
|
| タイトル |
Differential responses of Bcl-2 family genes to etoposide in chronic myeloid leukemia K562 cells.
|
| ジャーナル |
Mol Cell Biochem
|
| Abstract |
Etoposide is a potent anticancer agent that is used to treat various tumors. We have investigated the dose-dependent effect of etoposide on apoptosis using chronic myeloid leukemia K562 cells treated with low (5 microM) or high (100 microM) concentrations of the drug. At a low concentration, etoposide induced little apoptosis at 24 h, while about 20% of the cells showed apoptosis morphologically at a high concentration. Processing of caspase-3 was slightly detected from 12 h and became obvious at 24 h with 100 microM etoposide. Caspase-3-like protease activity was detected at 24 h with a high concentration. Moreover, these changes were accompanied by cleavage of poly ADP ribose polymerase (PARP). Changes of the mRNA levels of most apoptosis-regulating genes were not prominent at both concentrations, except for the rapid induction of c-IAP-2/HIAP-1 and the down-regulation of Bcl-X(L) by 100 microM etoposide. The downregulation of Bcl-X(L) protein occurred from 6 h, while Bax protein conversely showed a slight increase from 6 h. Taken together, the present findings show that the dose-dependent apoptotic effect of etoposide is based on a change in the balance between Bcl-X(L) and Bax, which precedes the activation of caspase-3.
|
| 巻・号 |
206(1-2)
|
| ページ |
43-50
|
| 公開日 |
2000-3-1
|
| DOI |
10.1023/a:1007056727876
|
| PMID |
10839193
|
| MeSH |
Antineoplastic Agents, Phytogenic / pharmacology*
Apoptosis / drug effects
Caspase 3
Caspases / metabolism
DNA Damage / drug effects
DNA Primers / chemistry
DNA, Neoplasm / drug effects
Dose-Response Relationship, Drug
Down-Regulation
Etoposide / pharmacology*
Gene Expression Regulation
Genes, bcl-2 / drug effects*
Humans
Immunoblotting
K562 Cells / drug effects*
K562 Cells / metabolism
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
Microscopy, Fluorescence
Poly (ADP-Ribose) Polymerase-1
Poly(ADP-ribose) Polymerases
Proteins / metabolism
Proto-Oncogene Proteins / genetics
Proto-Oncogene Proteins / metabolism*
Proto-Oncogene Proteins c-bcl-2 / genetics
Proto-Oncogene Proteins c-bcl-2 / metabolism*
RNA, Messenger / metabolism
Reverse Transcriptase Polymerase Chain Reaction
bcl-2-Associated X Protein
bcl-X Protein
|
| IF |
2.795
|
| 引用数 |
17
|
|
WOS 分野
|
CELL BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
|
