| RRC ID |
39325
|
| 著者 |
Yamamoto C, Takemoto H, Kuno K, Yamamoto D, Tsubura A, Kamata K, Hirata H, Yamamoto A, Kano H, Seki T, Inoue K.
|
| タイトル |
Cycloprodigiosin hydrochloride, a new H(+)/Cl(-) symporter, induces apoptosis in human and rat hepatocellular cancer cell lines in vitro and inhibits the growth of hepatocellular carcinoma xenografts in nude mice.
|
| ジャーナル |
Hepatology
|
| Abstract |
The effects of cycloprodigiosin hydrochloride (cPrG-HCl), a new H(+)/Cl(-) symporter, were examined in liver cancer cell lines in vitro and in vivo. In the in vitro MTT assay, cPrG-HCl inhibited the growth of 6 liver cancer cell lines (Huh-7, HCC-M, HCC-T, dRLh-84, and H-35, hepatocellular carcinoma; HepG2, hepatoblastoma) in a dose- and time-dependent manner. The 50% inhibitory concentrations (IC(50)) at 72 hours' treatment for liver cancer cell lines were 276 to 592 nmol/L, while that for isolated normal rat hepatocyte was 8.4 micromol/L. The cPrG-HCl treatment of Huh-7 cells induced apoptosis as confirmed by the appearance of a subG(1) population, intranucleosomal DNA fragmentation, and chromatin condensation. cPrG-HCl raised the pH of acidic organelles and lowered pHi (below pH 6.8). In addition, the apoptosis in Huh-7 cells induced by cPrG-HCl was strongly suppressed when the cells were cultured with imidazole, a cell-permeable base. In the in vivo assay, nude mice bearing subcutaneous xenografted Huh-7 cells received 2 weeks of treatment with cPrG-HCl (1 or 10 mg/kg/d) subcutaneously. This treatment significantly inhibited tumor growth compared with the control after 8 days. The control mice were treated with 1% dimethylsulfoxide (DMSO) in saline (vehicle). A histopathological examination using the terminal deoxynucleotidyl transferase mediated dUTP biotin nick end labeling (TUNEL) method showed apoptosis in the treated tumor cells. No pathological changes were observed in any organs, and the serum alanine transaminase levels remained within normal limits. These results suggest that cPrG-HCl may be useful for the treatment of hepatocellular carcinoma.
|
| 巻・号 |
30(4)
|
| ページ |
894-902
|
| 公開日 |
1999-10-1
|
| DOI |
10.1002/hep.510300417
|
| PII |
S0270913999004383
|
| PMID |
10498640
|
| MeSH |
Animals
Antiporters / pharmacology*
Apoptosis*
Carcinoma, Hepatocellular / pathology*
Cell Division / drug effects
Humans
Hydrogen-Ion Concentration
Indoles / pharmacology*
Liver Neoplasms / pathology*
Mice
Mice, Nude
Microscopy, Fluorescence
Neoplasm Transplantation*
Pyrroles / pharmacology*
Rats
Transplantation, Heterologous*
Tumor Cells, Cultured / drug effects
|
| IF |
14.679
|
| 引用数 |
101
|
|
WOS 分野
|
GASTROENTEROLOGY & HEPATOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
HuH-7(RCB1366)
Hep G2(RCB0459) |
