| RRC ID |
58023
|
| 著者 |
Tang R, Kimishima A, Ishida R, Setiawan A, Arai M.
|
| タイトル |
Selective cytotoxicity of epidithiodiketopiperazine DC1149B, produced by marine-derived Trichoderma lixii on the cancer cells adapted to glucose starvation.
|
| ジャーナル |
J Nat Med
|
| Abstract |
The core of solid tumors is characterized by hypoxia and a nutrient-starved microenvironment and has gained much attention as targets of anti-cancer drugs. In the course of search for selective growth inhibitors against the cancer cells adapted to nutrient starvation, epidithiodiketopiperazine DC1149B (1) together with structurally related compounds, trichodermamide A (2) and aspergillazine A (3), were isolated from culture extract of marine-derived Trichoderma lixii. Compounds 1 exhibited potent selective cytotoxic activity against human pancreatic carcinoma PANC-1 cells cultured under glucose-starved conditions with IC50 values of 0.02 µM. The selective index of the compound 1 was found to be 35,500-fold higher for cells cultured under glucose-starved conditions than those under the general culture conditions. The mechanistic analysis indicated that compound 1 inhibited the response of the ER stress signaling. In addition, these effects of compound 1 could be mediated by inhibiting complex II in the mitochondrial electron transport chain.
|
| 巻・号 |
74(1)
|
| ページ |
153-158
|
| 公開日 |
2020-1-1
|
| DOI |
10.1007/s11418-019-01357-w
|
| PII |
10.1007/s11418-019-01357-w
|
| PMID |
31435860
|
| PMC |
PMC7946679
|
| MeSH |
Antineoplastic Agents / pharmacology*
Cell Line, Tumor
Dipeptides / chemistry
Dipeptides / pharmacology*
Electron Transport / drug effects
Glucose / metabolism
Growth Inhibitors / pharmacology
Humans
Mitochondria / metabolism
Neoplasms / drug therapy*
Piperazines / pharmacology*
Trichoderma / chemistry*
Tumor Microenvironment
|
| IF |
2.055
|
| 引用数 |
4
|
| リソース情報 |
| ヒト・動物細胞 |
PANC-1(RCB2095) |
