| RRC ID |
59937
|
| 著者 |
Matsumoto T, Jimi S, Migita K, Terada K, Mori M, Takamatsu Y, Suzumiya J, Hara S.
|
| タイトル |
FF-10501 induces caspase-8-mediated apoptotic and endoplasmic reticulum stress-mediated necrotic cell death in hematological malignant cells.
|
| ジャーナル |
Int J Hematol
|
| Abstract |
FF-10501 is a novel inhibitor of inosine monophosphate dehydrogenase (IMPDH). Clinical trials of FF-10501 for myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are currently being conducted in the United States. Although it has been shown that FF-10501 induces apoptosis in hematological malignant cells, the intracellular mechanisms of this effect have not been characterized. We conducted an in vitro study to elucidate the mechanisms of FF-10501-induced cell death using 12 hematological malignant cell lines derived from myeloid and lymphoid malignancies. FF-10501 suppressed the growth of each cell line in a dose-dependent manner. However, the clinically relevant dose (40 μM) of FF-10501 induced cell death in three cell lines (MOLM-13, OCI-AML3, and MOLT-3). Investigation of the cell death mechanism suggested that FF-10501 induces both apoptotic and necrotic cell death. FF-10501-induced apoptosis was mediated by caspase-8 activation followed by activation of the mitochondrial pathway in MOLM-13 and MOLT-3 cells. FF-10501 induced necrotic cell death via endoplasmic reticulum stress in OCI-AML3 cells. The present study is the first to identify intracellular pathways involved in FF-10501-induced cell death.
|
| 巻・号 |
110(5)
|
| ページ |
606-617
|
| 公開日 |
2019-11-1
|
| DOI |
10.1007/s12185-019-02722-x
|
| PII |
10.1007/s12185-019-02722-x
|
| PMID |
31407254
|
| MeSH |
Apoptosis / drug effects
Caspase 8 / metabolism
Cell Death / drug effects*
Cell Line, Tumor
Endoplasmic Reticulum Stress
Enzyme Inhibitors / pharmacology
Enzyme Inhibitors / therapeutic use
Hematologic Neoplasms / pathology*
Humans
IMP Dehydrogenase / antagonists & inhibitors*
Mitochondria / metabolism
Necrosis / chemically induced
|
| IF |
2.251
|
| 引用数 |
0
|
| リソース情報 |
| ヒト・動物細胞 |
HL-60 |
