Abstract
African American women are more prone to develop breast cancer at a younger age and present with a more aggressive, hormone-independent form of the disease than those belonging to other ethnic groups. Currently there are limited targeted pharmacologic therapies for this type of breast cancer. Both Aminoflavone (NSC 686288) and 5F-203 (2-(4-Amino-3-methylphenyl)-5-fluorobenzothiazole) have shown promise as potential new pharmacologic options. The purpose of our study is to determine whether the antioxidants luteolin, resveratrol, and tempol differentially perturb the growth inhibitory effects of aminoflavone- and 5F-203-treatment in a panel of MCF-7, CRL 2335, and MDA-MB-468 breast cancer cells. The CRL 2335 and MDA-MB-468 cells are derived from African-American patients and are estrogen receptor and progesterone receptor negative while the MCF-7 cell line is derived from a Caucasian patient and is estrogen receptor and progesterone receptor positive. The results from Alamar Blue™ reduction assays show that in MCF-7 cells the antioxidants (1 M-1mM) caused a dose-dependent increase in Aminoflavone-mediated growth suppression, while the antioxidants (1 M-10 M) caused a dose-dependent decrease in 5F-203-mediated growth suppression. In contrast, the antioxidants had a lesser effect on the growth of CRL-2335 cells and MDA-MB-468 that were treated with Aminoflavone or 5F-203. These results were confirmed by phase-contrast microscopy of the cell lines and correlated to changes in the number of sub-G1 cells observed by flow cytometry. The results suggest that the antioxidant milieu of breast cancer cells may be important to differential drug-response. Further studies are currently underway to correlate these observed responses to differential changes in glutathione levels along with quantitative RT2-PCR analysis of changes in expression of oxidative stress-responsive genes.
Second AACR International Conference on the Science of Cancer Health Disparities— Feb 3–6, 2009; Carefree, AZ
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