In vitro and in vivo multidrug resistance reversal activity by a Betti-base derivative of tylosin.
Br J Cancer
; 103(2): 178-85, 2010 Jul 13.
Article
in En
| MEDLINE
| ID: mdl-20551959
ABSTRACT
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-alpha-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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Doxorubicin
/
Tylosin
/
ATP Binding Cassette Transporter, Subfamily B, Member 1
/
Drug Resistance, Multiple
/
Drug Resistance, Neoplasm
/
Lactones
/
Naphthols
Type of study:
Evaluation_studies
Limits:
Animals
Language:
En
Journal:
Br J Cancer
Year:
2010
Document type:
Article
Affiliation country:
Hungary