RRC ID |
43953
|
著者 |
Tazawa Y, Matsumura K, Takekuma Y, Sugawara M.
|
タイトル |
Schedule-dependent cytotoxicity of etoposide (VP-16) and cyclophosphamide in leukemia cell line K-562.
|
ジャーナル |
Biol Pharm Bull
|
Abstract |
In allogeneic bone marrow transplantation (allo-BMT) in patients with leukemia, the combination of VP-16 and cyclophosphamide (CY) is commonly used for the conditioning regimen. In the present study, we demonstrated schedule-dependent cytotoxicity of VP-16 and CY in K-562 cells. K-562 cells were pretreated with low concentrations (2.5 and 5 µg/mL) of 4-hydroperoxycyclophosphamide (40487S), which is a preactivated analog of CY. It was confirmed that these concentrations did not influence cell viability. Cells subsequently exposed to 0.5-100 µg/mL of VP-16 showed reduced the viability compared to that of control cells not treated with 40487S. In contrast, there was no change in the viability of K-562 cells pretreated with low concentrations (0.5 and 1 µg/mL) of VP-16. It was confirmed that these concentrations did not influence cell viability. Viability of subsequently exposed to 1-20 µg/mL was not different from that of control cells not treated with VP-16. VP-16 caused cell cycle arrest at G₂/M phase. On the other hand, 40487S arrested the cell cycle at S phase. Thymidine-synchronized cells, VP-16 showed cell cycle specificity for cell killing from early-S to mid-S phase. On the other hand, 40487S showed cell cycle-independent cytotoxicity. Exposure of cells to VP-16 after 40487S induced a greater cytotoxic effect on K-562 cells. The findings may lead to improvements in clinical combination chemotherapy.
|
巻・号 |
35(7)
|
ページ |
1132-6
|
公開日 |
2012-1-1
|
DOI |
10.1248/bpb.b12-00159
|
PII |
DN/JST.JSTAGE/bpb/b12-00159
|
PMID |
22791162
|
MeSH |
Antineoplastic Agents, Alkylating / administration & dosage*
Antineoplastic Agents, Phytogenic / administration & dosage*
Cell Cycle / drug effects
Cell Survival / drug effects
Cyclophosphamide / administration & dosage*
Drug Administration Schedule
Etoposide / administration & dosage*
Humans
K562 Cells
Leukemia
|
IF |
1.863
|
引用数 |
2
|
WOS 分野
|
PHARMACOLOGY & PHARMACY
|
リソース情報 |
ヒト・動物細胞 |
K-562(RCB1635) |