Publication Date

Fall 2016

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Biological Sciences

Advisor

Brandon White

Keywords

Breast Cancer, Flavonoids, Quercetin

Subject Areas

Biology

Abstract

Quercetin is a member of the flavonoid family, found in fruits and vegetables, and has

shown cytotoxic effects on many cancers, including breast cancer. Quercetin’s methylated derivatives, 3-O-methyl quercetin, pentamethyl quercetin, isorhamnetin, and tamarixetin, differ in their substitution patterns of the methyl capping at the 5-hydroxyl groups. Cell death assays performed on MDA-MB-231 cells showed increased cytotoxicity with quercetin and all its methylated derivatives, except pentamethyl quercetin, after 72 hours of treatment. Loss of the mitochondrial outer membrane potential (MOMP) was seen using a JC-1 assay after 15 min incubation with compounds, except for pentamethyl quercetin. We saw no change in MOMP after 24 hours of treatment with all quercetin derivatives. Treatment with compounds showed no change in intracellular reactive oxygen species (ROS). However, the generation of ROS by TBHP, positive control, was decreased after treatment, indicating that these compounds can function as an anti-oxidant by decreasing cellular ROS. The quercetin derivatives showed cell cycle arrest at various phases. Our data from the cell viability assay suggest that a structure-function relationship exists between methylation of the hydroxyl groups available on the quercetin molecule and its cytotoxicity in breast cancer cells, where the presence of at least one hydroxyl group is necessary for the compound to exert a cytotoxic effect.

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