Date of Award

2013

Document Type

Thesis

First Advisor

Rorie, Checo J.

Abstract

Triple Negative Breast Cancer (TNBC) is a rare basal-like subtype of breast cancer characterized by the absence of the estrogen (ER), progesterone (PR), and human epidermal receptor 2 (HER2) receptors which are normally targeted in other breast cancer subtypes, thereby making TNBC difficult to combat. In this study, four different styrene compounds (1.001, 1.006, 1.007, and 1.009) were used to treat TNBC cell lines HCC1806 and HCC70. Each of the compounds were composed of a 3-nitro group on the A ring and varying aryl groups on the B ring of the styrene. The breast cancer cells were exposed over a 24-hour period to a 10, 100 and 1000 μM styrene concentration. Styrene compounds have a similar structural composition to Resveratrol and some known Poly (adenosine diphosphate (ADP)-ribose) Polymerase (PARP) inhibitors. Previous studies have demonstrated that PARP-1 has a high affinity for breast cancer susceptibility gene-deficient (BRCA) breast carcinomas such as TNBC. Similarities in structure suggest that these compounds may have the same apoptotic effect found in PARP inhibitors used in treating cancer. A cell viability assay revealed that all of the styrene compounds were effective and showed apoptosis at varying concentrations in-vitro. Apoptosis was also verified with phase-contrast microscopy and Methylthiazol Tetrazolium (MTT) Assay. PARP inhibition by styrenyl compounds was verified with the HT Fluorescent Homogenous PARP Inhibition Assay. Preliminary data show that these compounds have the ability to induce apoptosis in triple negative cells and lead us to believe these compounds represent a novel potential chemotherapeutic treatment for TNBC.

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