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 β subunit. There are many isotypes of β-tubulin and their distributions differ among different tissues. The βIII 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 βIII 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 βIII in a xenogeneic mouse model. We found that CH-35 was as toxic as Taxol® in vivo. Although the βIII-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.
Keywords: Anti-tumor agent; Breast cancer; Colchicine binding; In vitro; In vivo; Tubulin.