Date of Award
Chemistry and Biochemistry
The traditional perspective of Histone Deacetylase enzymes is focused on their inherent epigenetic modification characteristics. While it is true that the histone modification these enzymes exhibit play a role in cancer and related diseases, Histone Deacetylase has a variety of non-histone targets. The non-histone targets include microtubules and are of specific interest because of the microtubules’ role in cell line differentiation, replication, apoptosis, and cancer metastasis. Using a variety of Histone Deacetylase Inhibitors (HDACi) and other chemotherapeutic compounds, our research group explored the HDACi effect on breast cancer cell lines. Our goal was to indicate the presence of HDACi cell-line dependent cancer growth inhibition and to study the hypothesized non-histone mechanism of microtubule modification in HDACi(s). The experiment consisted of three parts: viability assay, clonogenic assay, and combination assay which analyzed HDACi(s) possible synergistic character with microtubule-stabilizing compounds. The specific breast cancer cell lines used were MDA-MB-231 clones LM-4175 and BOM-1833, and MCF7-BOM. The results of our experiments indicated that there was cell line dependent growth inhibition with the treatment of HDACi(s). Specifically, MCF7-BOM showed to be more susceptible to treatment, and this could be due to it being an estrogen receptor positive ER+ cell line. However, the growth inhibition never reached complete inhibition and was most prominent at the highest concentrations of HDACi(s). Higher concentrations of HDACi(s) also had the most prominent effect on colony growth inhibition in the clonogenic assay. The combination assay had an interesting result indicating an antagonistic trend between microtubule stabilizers and HDACi(s).
Sistrunk, William E., "Histone Deacetylase Inhibitors and Breast Cancer Metastasis: A Review and Exploration of HDAC(i)s and Other Chemotherapeutic Agents" (2019). Honors Theses. 1242.