Effect of CH-35, a novel anti-tumor colchicine analogue, on breast cancer cells overexpressing the ßIII isotype of tubulin.
Invest New Drugs
; 34(1): 129-37, 2016 Feb.
Article
in En
| MEDLINE
| ID: mdl-26686345
ABSTRACT
The subunit protein of microtubules is tubulin, which has been the target for some of the most successful and widely used anti-tumor drugs. Most of the drugs that target tubulin bind to the ß subunit. There are many isotypes of ß-tubulin and their distributions differ among different tissues. The ßIII isotype is over-expressed in many tumors, particularly those that are aggressive, metastatic, and drug resistant. We have previously reported the design and synthesis of a series of compounds to fit the colchicine site on ßIII but not on the other isotypes. In the current study, we tested the toxicity and the anti-tumor activity of one of these compounds, CH-35, on the human breast tumor MDA-MB-231 over-expressing ßIII in a xenogeneic mouse model. We found that CH-35 was as toxic as Taxol® in vivo. Although the ßIII-over-expressing cells developed into very fast-growing tumors, CH-35 was more effective against this tumor than was Taxol. Our results suggest that CH-35 is a promising candidate for future drug development.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Tubulin
/
Breast Neoplasms
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Colchicine
/
Antineoplastic Agents
Limits:
Animals
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Female
/
Humans
Language:
En
Journal:
Invest New Drugs
Year:
2016
Document type:
Article