Sophia Kekchidou


Investigating the Mechanism of Action Behind Novel Anti-Cancer Drugs

Microtubules serve as a fundamental component of the cytoskeleton. Due to the nature of their role in cell division, microtubules are important targets for potential chemotherapy drugs. I am in the process of attempting to determine the mechanism of action of fluorinated benzylidene indanone 1 (Ind-V). Ind-V was derived from chemical modification of the plant-derived compound gallic acid. Ind-V contains the trimethoxy ring structure that is key to the microtubule-depolymerizing activity of the drug colchicine, which is currently used to treat gout. I found that, like colchicine, Ind-V inhibits the division of cells by arresting them in mitosis. I used three cell-based assays to test the effects of Ind-V on HeLa cells, a cervical cancer cell line. Unlike colchicine, Ind-V did not promote microtubule depolymerization and instead generated mitotic spindle abnormalities very similar to those generated by the microtubule-stabilizing anticancer drug, Taxol. The drug likewise failed to inhibit microtubule polymerization in an in vitro assay involving purified bovine brain tubulin. An unusual light scattering pattern was recorded in the in vitro assay, suggesting that Ind-V may have a unique effect on microtubules.

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