Author

Erika Knott

Date of Award

2014

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Biological Sciences

Committee Chair

Debra M. Moriarity

Committee Member

Luis R. Cruz-Vera

Committee Member

John W. Shriver

Committee Member

William N. Setzer

Subject(s)

DNA topoisomerases, Caffeine--Physiological effect, Pharmacognosy, Antineoplastic agents

Abstract

The essential nature of topoisomerase II makes it an ideal target for anticancer drugs. Such anticancer agents may either interfere with the catalytic activity of the enzyme, or cause it to induce permanent double-stranded breaks in the DNA. In this study, ten anticancer agents (berberine, chelerythrine, doxorubicin, sanguinarine, tingenone, paclitaxel, malvidin, delphinidin, ellipticine, and pelargonidin) were studied through gel electrophoresis assays to determine their ability to inhibit topoisomerase II activity. Caffeine has been shown to reduce the effectiveness of some topoisomerase II-targeting anticancer drugs. This ability was evaluated by the addition of caffeine in concentrations ranging from 165 nM to 50 mM. Caffeine was found to affect the intercalative ability of doxorubicin, sanguinarine, delphinidin, and ellipticine. Caffeine was also found to potentiate the effects of tingenone, delphinidin, and ellipticine, as well as the combination of berberine and delphinidin. When tested in combination, interactions between several drug pairs were observed.

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