| RRC ID |
45506
|
| 著者 |
Okuyama K, Kaida A, Hayashi Y, Hayashi Y, Harada K, Miura M.
|
| タイトル |
KPU-300, a Novel Benzophenone-Diketopiperazine-Type Anti-Microtubule Agent with a 2-Pyridyl Structure, Is a Potent Radiosensitizer That Synchronizes the Cell Cycle in Early M Phase.
|
| ジャーナル |
PLoS One
|
| Abstract |
KPU-300 is a novel colchicine-type anti-microtubule agent derived from plinabulin (NPI-2358). We characterized the effects of KPU-300 on cell cycle kinetics and radiosensitization using HeLa cells expressing the fluorescent ubiquitination-based cell cycle indicator (Fucci). Cells treated with 30 nM KPU-300 for 24 h were efficiently synchronized in M phase and contained clearly detectable abnormal Fucci fluorescence. Two-dimensional flow-cytometric analysis revealed a fraction of cells distinct from the normal Fucci fluorescence pattern. Most of these cells were positive for an M phase marker, the phosphorylated form of histone H3. Cells growing in spheroids responded similarly to the drug, and the inner quiescent fraction also responded after recruitment to the growth fraction. When such drug-treated cells were irradiated in monolayer, a remarkable radiosensitization was observed. To determine whether this radiosensitization was truly due to the synchronization in M phase, we compared the radiosensitivity of cells synchronized by KPU-300 treatment and cells in early M phase isolated by a combined method that took advantage of shake-off and the properties of the Fucci system. Following normalization against the surviving fraction of cells treated with KPU-300 alone, the surviving fractions of cells irradiated in early M phase coincided. Taken together with potential vascular disrupting function in vivo, we propose a novel radiosensitizing strategy using KPU-300.
|
| 巻・号 |
10(12)
|
| ページ |
e0145995
|
| 公開日 |
2015-1-1
|
| DOI |
10.1371/journal.pone.0145995
|
| PII |
PONE-D-15-29842
|
| PMID |
26716455
|
| PMC |
PMC4696839
|
| MeSH |
Benzophenones / pharmacology*
Cell Cycle / drug effects
Cell Division / drug effects*
Cell Line, Tumor
Diketopiperazines / pharmacology*
Flow Cytometry
Fluorescent Antibody Technique
HeLa Cells
Humans
Microtubules / drug effects*
Radiation-Sensitizing Agents / pharmacology*
|
| IF |
2.74
|
| 引用数 |
1
|
|
WOS 分野
|
ONCOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
HeLa/Fucci(RCB2812) |
