The Application of Non-Invasive Apoptosis Detection Sensor (NIADS) on Histone Deacetylation Inhibitor (HDACi)-Induced Breast Cancer Cell Death

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.

HDAC1 and HDAC2 Double Knockout Triggers Cell Apoptosis in Advanced Thyroid Cancer

“…In a previous study, we established a bioluminescence-based live cell noninvasive apoptosis detection sensor (NIADS) system to evaluate the quantitative and kinetic characteristics of apoptotic cell death [14]. Using this assay, we were able to determine apoptotic events by simply measuring the bioluminescence activity in live cells.…”

“…However, currently available quantitative apoptosis assays, such as the annexin V/FITC assay, require extensive sample handling and substantial labor for cell harvest and analysis. Therefore, a quantitative apoptosis assay with easy handling (the NIADS assay) was established in our previous study [14], with notable advantages, such as relatively low cell numbers, trace amounts of bioluminescence, viral infection and quick assay. These unique strengths make apoptosis detection assays suitable for high-throughput cell-based screening of drug libraries and related applications.…”

“…Further epigenetic alterations involved in cell cycle arrest and apoptosis were also investigated. Using our developed techniques, which combine lentiviral transfection and noninvasive apoptosis detection sensor (NIADS) analysis [14], we were able to quantitatively and kinetically analyze apoptotic cell death in HDACi-treated SW579 cells. HDAC1 and HDAC2 are two of the most investigated proteins in balancing histone acetylation and chromatin remodeling.…”

Androgen Receptor in Breast Cancer: From Bench to Bedside

“…Although such patients can benefit from treatment targeting the ER or HER2, ER+ BC frequently acquires resistance to endocrine therapy ( 5 ). Triple-negative BC (TNBC), which lacks the expression of ER, PR, and HER2, constitutes 15–20% of BC cases, and has the highest probability of metastasis and the lowest overall survival (OS) among all BC subtypes ( 6 , 7 ). Currently, there is no well-defined targeted therapy for TNBC ( 8 ).…”

HDAC1,2 Knock-Out and HDACi Induced Cell Apoptosis in Imatinib-Resistant K562 Cells

“…In the clinic, five FDA-approved HDACis have been used against peripheral T-cell lymphoma, multiple myeloma or even bipolar disorders [7]. For other chemotherapies, HDACis provide optimal benefits in combinatory schedules, showing high therapeutic efficacy on cancer therapy, such as triple negative breast cancer [8,9] and acute myeloid leukemia [10].…”