Abstract
Breast cancer is the most common malignancy in women and the second leading cause of cancer death in women. Triple negative breast cancer (TNBC) subtype is a breast cancer subset without ER (estrogen receptor), PR (progesterone receptor) and HER2 (human epidermal growth factor receptor 2) expression, limiting treatment options and presenting a poorer survival rate. Thus, we investigated whether histone deacetylation inhibitor (HDACi) could be used as potential anti-cancer therapy on breast cancer cells. In this study, we found TNBC and HER2-enriched breast cancers are extremely sensitive to Panobinostat, Belinostat of HDACi via experiments of cell viability assay, apoptotic marker identification and flow cytometry measurement. On the other hand, we developed a bioluminescence-based live cell non-invasive apoptosis detection sensor (NIADS) detection system to evaluate the quantitative and kinetic analyses of apoptotic cell death by HDAC treatment on breast cancer cells. In addition, the use of HDACi may also contribute a synergic anti-cancer effect with co-treatment of chemotherapeutic agent such as doxorubicin on TNBC cells (MDA-MB-231), but not in breast normal epithelia cells (MCF-10A), providing therapeutic benefits against breast tumor in the clinic.
Highlights
Epigenetic modifications play a crucial role in chromatin remodeling of cancer hallmarks [1]
We investigated whether histone deacetylation inhibitor (HDACi) could be used as a potential anti-cancer therapy on breast cancer cells
We developed a bioluminescence-based live cell apoptosis detection assay by split-luciferase fragment system through lentivirus transfection
Summary
Epigenetic modifications play a crucial role in chromatin remodeling of cancer hallmarks [1]. When histone is acetylated by histone acetyl-transferases (HATs) on the tail end, histones become negatively charged and are associated with a looser chromatin state and gene-transcription activation. Histone acetylation is modulated by histone deacetylases (HDACs) and is associated with a tighter chromatin state and gene transcriptional silencing [3]. This type of epigenetic regulation plays a pivotal role in tumor biology, as tumor cells tend to manipulate selective gene expression in order to facilitate survival [1,4]
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