| Autor: |
Wright, Paul S., Cross-Doersen, Doreen, Th'ng, John P.H., Guo, Xiao-Wen, Crissman, Harry A., Bradbury, E.Morton, Montgomery, Lauren R., Thompson, Felisa Y., Loudy, David E., Johnston, J.O'Neal, Bitonti, Alan J. |
| Zdroj: |
Experimental Cell Research; January 1996, Vol. 222 Issue: 1 p54-60, 7p |
| Abstrakt: |
MDL 101,731, (E)2′-fluoromethylene-2′-deoxycytidine, is an irreversible inhibitor of ribonucleotide diphosphate reductase and causes regression of human tumors in nude mouse models. Messenger RNA levels for testosterone-repressed prostatic message-2 (TRPM-2), a transcript that increases in human tumor xenografts undergoing programmed cell death, were analyzed byin situhybridization. Xenografts derived from a human prostate tumor cell line (PC-3) regressed following treatment with MDL 101,731 and the relative levels of TRPM-2 mRNA increased up to threefold in drug-treated animals. Apoptosis in the tumor xenografts was further indicated byin situlabeling of DNA strand breaks by incorporation of biotinylated-dUTP with terminal deoxynucleotidyl transferase.In vitro,PC-3 cells incubated with MDL 101,731 showed evidence of apoptosis based on flow cytometry and DNA laddering. These data support the hypothesis that MDL 101,731 stimulates programmed cell death in regressing PC-3 xenografts. |
| Databáze: |
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