Honors Program

Midway Honors

Date of Award

5-2013

Thesis Professor(s)

Victoria Ramsauer

Thesis Professor Department

Pharmaceutical Sciences

Thesis Reader(s)

Allan Forsman, Cerrone Foster

Abstract

Flavonoids are ubiquitous to all terrestrial plants and many are known to have anti-tumor activities. In this research project we studied the differential cytotoxic effects of two flavone isomers on human breast cancer cells (BT-474, SKBR-3, and MCF-7) and normal breast cells as a control (MCF-10A). The basis of the relationships between chemical structures, type and position of substituent groups and the effects these compounds exert specifically on cancer cells are not completely elucidated. These flavones are derived from plants native of Colombia, South America. These plants of the family Asteraceae, genera Gnaphalium and Achyrocline are reputed to have anti-cancer properties. The flavones are non-toxic to normal human cells. Our studies indicate that 3,5-dihydroxy-6,7,8-trimethoxy-2-phenyl-4H-chromen-4-one (3,5-dihydroxy-6,7,8-trimethoxy flavone, flavone B) is highly cytotoxic to poorly differentiated carcinomas of the breast such as SK-BR3, with minimal activity against more differentiated carcinomas of the same organs such BT-474. Immunoblot analysis suggests that the anti-tumor effects of flavone B in SKBR-3 may be mediated through the down regulation of the ERK pathway. ERK activation promotes cell proliferation, differentiation and survival. Additionally, flavone B down regulates PS6 in SKBR-3. PS6 controls protein translation by phosphorylating the S6 protein of the 40S ribosomal subunit. On the other hand, neither flavone A or B has a significant inhibitory effect on breast cancer cell line BT-474. The flavones were tested in the human fibrocystic mammary tissue MFC-10A, defined as a normal breast cell line, to demonstrate their lack of toxicity against normal cells.

Document Type

Honors Thesis - Withheld

Copyright

Copyright by the authors.

Share

COinS