原创力文档selective targeting of tumorigenic cancer cell lines by microtubule inhibitors有选择性的针对肿瘤发生的癌症细胞系的微管抑制剂.pdfVIP
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selective targeting of tumorigenic cancer cell lines by microtubule inhibitors有选择性的针对肿瘤发生的癌症细胞系的微管抑制剂
Selective Targeting of Tumorigenic Cancer Cell Lines by
Microtubule Inhibitors
1 1,3 2,3
Newaj M. Abdullah , Gus R. Rosania *, Kerby Shedden *
1 Department of Pharmaceutical Sciences, University of Michigan College of Pharmacy, Ann Arbor, Michigan, United States of America, 2 Department of Statistics,
University of Michigan, Ann Arbor, Michigan, United States of America, 3 Michigan Alliance for Cheminformatics Exploration (MACE), Ann Arbor, Michigan, United States of
America
Abstract
For anticancer drug therapy, it is critical to kill those cells with highest tumorigenic potential, even when they comprise a
relatively small fraction of the overall tumor cell population. We have used the established NCI/DTP 60 cell line growth
inhibition assay as a platform for exploring the relationship between chemical structure and growth inhibition in both
tumorigenic and non-tumorigenic cancer cell lines. Using experimental measurements of ‘‘take rate’’ in ectopic implants as a
proxy for tumorigenic potential, we identified eight chemical agents that appear to strongly and selectively inhibit the
growth of the most tumorigenic cell lines. Biochemical assay data and structure-activity relationships indicate that these
compounds act by inhibiting tubulin polymerization. Yet, their activity against tumorigenic cell lines is more selective than
that of the other microtubule inhibitors in clinical use. Biochemical differences in the tubulin subunits that make up
microtubules, or differences in the function of microtubules in mitotic spindle assembly or cell division may be associated
with the selectivity of these compounds.
Citation: Abdullah NM, Rosania GR, Shedden K (2009) Selective Targeting of Tum
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