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

Int J Mol Sci. 2018 Feb 2;19(2):452. doi: 10.3390/ijms19020452.

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.

Keywords: HDACi; live cell non-invasive apoptosis detection sensor (NIADS); triple negative breast cancer (TNBC).

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Biological Assay*
  • Cell Line, Tumor
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Female
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic*
  • Histone Deacetylase Inhibitors / pharmacology*
  • Histone Deacetylases / genetics*
  • Histone Deacetylases / metabolism
  • Humans
  • Hydroxamic Acids / pharmacology*
  • Indoles / pharmacology*
  • Mammary Glands, Human / drug effects
  • Mammary Glands, Human / metabolism
  • Mammary Glands, Human / pathology
  • Panobinostat
  • Receptor, ErbB-2 / deficiency
  • Receptor, ErbB-2 / genetics
  • Receptors, Estrogen / deficiency
  • Receptors, Estrogen / genetics
  • Receptors, Progesterone / deficiency
  • Receptors, Progesterone / genetics
  • Sulfonamides / pharmacology*
  • Triple Negative Breast Neoplasms / drug therapy
  • Triple Negative Breast Neoplasms / genetics
  • Triple Negative Breast Neoplasms / metabolism
  • Triple Negative Breast Neoplasms / pathology

Substances

  • Antineoplastic Agents
  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • Indoles
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Sulfonamides
  • Panobinostat
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Histone Deacetylases
  • belinostat