Date of Award
Chemistry and Biochemistry
Dale G. Nagle
Histone deacetylase enzymes are known for their inherent activity as epigenetic modifiers. Although, they have become recognized for their role in cancer progression and other diseases. But also, histone deacetylases have other non-histone targets, for example, microtubules, which play important roles in cancer metastasis, apoptosis, and replication. With histone deacetylase inhibitors (HDACi), our research explored HDACi effects on breast cancer cell lines. The overall goal was to understand the potential of largazole, a class one histone deacetylase inhibitor on breast cancer cell lines. The research consisted of two parts: sulforhodamine B (SRB) viability assays under hypoxic and normoxic conditions. The specific cell lines that were used were MCF-7, MCF-7 BoM, MDA-MB-231, and MDA-MB-231 BoM. The results of the experiments showed that histone deacetylase inhibitors, specifically Largazole is a useful chemotherapeutic agent against breast cancer. Also, Hypoxic conditions in combination with cycloheximide did lead to lower cell proliferation. The MCF-7 and MDA-231 had greater inhibition in normoxic condition. The BoM cell lines had greater inhibition in both conditions. And as expected the triple-negative did require a greater largazole concentration for effect to take place in the hypoxic conditions. The extremely aggressive cancer cell-line MDA-MB-231 gave the most conclusive results.
Carson, Hannah Lynn, "The Histone Deacetylase Inhibitor Largazole: A Potential Chemotherapeutic Agent" (2020). Honors Theses. 1405.
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