In vitro and in vivo multidrug resistance reversal activity by a Betti-base derivative of tylosin
BACKGROUND: The multidrug resistance (MDR) proteins are present in a majority of human tumours. Their activity is important to understand the chemotherapeutic failure. A search for MDR-reversing compounds was conducted among various Betti-base derivatives of tylosin. METHODS: Here, we evaluate the i...
Elmentve itt :
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| Dokumentumtípus: | Cikk |
| Megjelent: |
2010
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| Sorozat: | BRITISH JOURNAL OF CANCER
103 No. 2 |
| Tárgyszavak: | |
| doi: | 10.1038/sj.bjc.6605716 |
| mtmt: | 1365862 |
| Online Access: | http://publicatio.bibl.u-szeged.hu/38829 |
| Tartalmi kivonat: | BACKGROUND: The multidrug resistance (MDR) proteins are present in a majority of human tumours. Their activity is important to understand the chemotherapeutic failure. A search for MDR-reversing compounds was conducted among various Betti-base derivatives of tylosin. METHODS: Here, we evaluate the in vitro and in vivo P-glycoprotein (P-gp)-modulating activity of the most promising compound N-tylosil-1-a-amino-(3-bromophenyl)-methyl-2-naphthol (TBN) using human MDR1 gene-transfected and parental L5178 mouse lymphoma cell lines. RESULTS: In vitro experiments showed that TBN dramatically increased the P-gp-mediated cellular uptake of the fluorescent substrate rhodamine 123. Similarly, TBN was found to act as a very potent enhancer of the cytotoxicity of doxorubicin on the resistant cell line. We also provide in vivo evidence using DBA/2 mice in support for an increased tumoural accumulation of doxorubicin, without affecting its tissue distribution, resulting in an enhanced antitumoural effect. CONCLUSION: Our results suggest that TBN is a potent modulator of the P-gp membrane pump and that the compound could be of clinical relevance to improve the efficacy of chemotherapy in MDR cancers. British Journal of Cancer (2010) 103, 178-185. doi: 10.1038/sj.bjc.6605716 www.bjcancer.com Published online 15 June 2010 (C) 2010 Cancer Research UK |
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| Terjedelem/Fizikai jellemzők: | 8 178-185 |
| ISSN: | 0007-0920 |