title: Effect of CH-35, a novel anti-tumor colchicine analogue, on breast cancer cells overexpressing the βIII isotype of tubulin.
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.
authors.affiliation: Department of Biochemistry, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA.
authors.forename: Lee-Chuan C
authors.initials: LC
authors.lastname: Yeh
authors.affiliation: Department of Biochemistry, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA.
authors.forename: Asok
authors.initials: A
authors.lastname: Banerjee
authors.affiliation: Department of Biochemistry, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA.
authors.forename: Veena
authors.initials: V
authors.lastname: Prasad
authors.affiliation: Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Jack A
authors.initials: JA
authors.lastname: Tuszynski
authors.affiliation: Oncovista Innovative Therapies, Inc., 14785 Omicron Dr, San Antonio, TX, 78245, USA.
authors.forename: Alexander L
authors.initials: AL
authors.lastname: Weis
authors.affiliation: Oncovista Innovative Therapies, Inc., 14785 Omicron Dr, San Antonio, TX, 78245, USA.
authors.forename: Tamas
authors.initials: T
authors.lastname: Bakos
authors.affiliation: Pathology Department, Virginia Hospital Center, 1701 N George Mason Dr, Arlington, VA, 22205, USA.
authors.forename: I-Tien
authors.initials: IT
authors.lastname: Yeh
authors.affiliation: Department of Biochemistry, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA.
authors.forename: Richard F
authors.initials: RF
authors.lastname: Ludueña
authors.affiliation: Department of Biochemistry, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA. leej@uthscsa.edu.
authors.forename: John C
authors.identifier: http://orcid.org/0000-0001-8707-4018
authors.initials: JC
authors.lastname: Lee
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000633:toxicity; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D003078:Colchicine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D017239:Paclitaxel / Q000494:pharmacology / Q000633:toxicity; D018675:Toxicity Tests; D014404:Tubulin / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; C000611958:CH-35 compound; C498585:TUBB3 protein, human; D014404:Tubulin; D017239:Paclitaxel; D003078:Colchicine
keywords: Anti-tumor agent; Breast cancer; Colchicine binding; In vitro; In vivo; Tubulin