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 journalArticle

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

Keywords

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

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Oncology

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    Yeh, L. C. C., Banerjee, A., Prasad, V., Tuszynski, J. A., Weis, A. L., Bakos, T., Yeh, I. T., Ludueña, R. F., & Lee, J. C. (2016). Effect of CH-35, a novel anti-tumor colchicine analogue, on breast cancer cells overexpressing the βIII isotype of tubulin. Investigational New Drugs, 34(1), 129-137. https://doi.org/10.1007/s10637-015-0315-6