LYP, a novel bestatin derivative, inhibits cell growth and suppresses APN/CD13 activity in human ovarian carcinoma cells more potently than bestatin
| Autor: | Yi Yuan, Xiao-Fan Zhang, Shu-Xiang Cui, Zu-Hua Gao, Wenfang Xu, Cui-Rong Zhao, Yan-Na Cheng, Xian-Jun Qu, Jianjun Gao, Wei Tang |
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| Rok vydání: | 2010 |
| Předmět: |
CD13 Antigens
Biology Cleavage (embryo) Flow cytometry Mice chemistry.chemical_compound Western blot Leucine Cell Line Tumor medicine Animals Humans Pharmacology (medical) Cell Proliferation Ovarian Neoplasms Pharmacology chemistry.chemical_classification medicine.diagnostic_test Cell growth Cell Membrane Esters Xenograft Model Antitumor Assays Molecular biology Enzyme Oncology chemistry Biochemistry Cell culture Female Trypan blue Growth inhibition |
| Zdroj: | Investigational New Drugs. 29:574-582 |
| ISSN: | 1573-0646 0167-6997 |
| Popis: | LYP is a bestatin dimethylaminoethyl ester which inhibits aminopeptidase N (APN/CD13). Our goal in this study was to evaluate LYP as a candidate compound for cancer treatment, beginning by studying its inhibitory effects on tumors and then comparing it to bestatin. Experiments were performed on human ovarian carcinoma (OVCA) ES-2 and SKOV-3 cell lines, which have high and low levels of APN/CD13 respectively. LYP effectively inhibited ES-2 cell growth as estimated by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and the trypan blue dye-exclusion test. LYP significantly suppressed APN/CD13 activity on the surface of ES-2 cells as measured by quantifying the enzymatic cleavage of the substrate L-leucine-p-nitroanilide. The inhibitory effects of LYP were greater than those of bestatin at the same concentrations. In contrast, LYP was a weak inhibitor of SKOV-3 cell growth, suggesting that LYP may inhibit ES-2 cell growth via suppression of APN/CD13. Inhibition of APN/CD13 expression was also demonstrated with immunofluorescent flow cytometry and Western blot analysis. Inhibitory effects of LYP were confirmed by using a mouse model in which LYP delayed the growth of ES-2 xenografts in mice after 2 weeks of LYP injections. Inhibition of APN/CD13 expression was demonstrated in the ES-2 xenografts using Western blot analysis. The inhibitory effects of LYP on the ES-2 xenografts were stronger than those of bestatin. These results suggest that LYP has a powerful inhibitory effect on the growth of OVCA cells and that the mechanism may be via a decrease in the expression of APN/CD13. |
| Databáze: | OpenAIRE |
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