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

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Summary

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.

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Acknowledgments

We acknowledge the support by US Army Medical Research grants W81XWH-10-1-0904 (BC097712 and BC097712P1) to RFL and JCL, respectively.

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Authors and Affiliations

  1. Department of Biochemistry, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA

    Lee-Chuan C. Yeh, Asok Banerjee, Veena Prasad, Richard F. Ludueña & John C. Lee

  2. Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada

    Jack A. Tuszynski

  3. Oncovista Innovative Therapies, Inc., 14785 Omicron Dr, San Antonio, TX, 78245, USA

    Alexander L. Weis & Tamas Bakos

  4. Pathology Department, Virginia Hospital Center, 1701 N George Mason Dr, Arlington, VA, 22205, USA

    I-Tien Yeh

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  1. Lee-Chuan C. Yeh
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Yeh, LC.C., Banerjee, A., Prasad, V. et al. Effect of CH-35, a novel anti-tumor colchicine analogue, on breast cancer cells overexpressing the βIII isotype of tubulin. Invest New Drugs 34, 129–137 (2016). https://doi.org/10.1007/s10637-015-0315-6

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