Effect of CH-35, a novel anti-tumor colchicine analogue, on breast cancer cells overexpressing the βIII isotype of tubulin

Lee Chuan C. Yeh, Asok Banerjee, Veena Prasad, Jack A. Tuszynski, Alexander L. Weis, Tamas Bakos, I. Tien Yeh, Richard F. Ludueña, John C. Lee

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)129-137
Number of pages9
JournalInvestigational New Drugs
Volume34
Issue number1
DOIs
StatePublished - Feb 1 2016
Externally publishedYes

Keywords

  • Anti-tumor agent
  • Breast cancer
  • Colchicine binding
  • In vitro
  • In vivo
  • Tubulin

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Pharmacology (medical)

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