Breast cancer is the most common malignancies 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, PR and HER2 expression, limiting treatment options and presenting a poorer survival rate. Thus, we investigated whether HDACi would be used as potential anti-cancer therapy on breast cancer cells. In this study, we found TNBC and HER2-enrich 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 (IADS) 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 be accompanied with chemotherapeutic agent such as doxorubicin to synergic drug sensitivity on TNBC cell (MDA-MB-231), but not in breast normal epithelia cells (MCF-10A), providing therapeutic benefits against breast tumor in clinic.

Diabetes mellitus (DM) is one of the principal manifestations of metabolic syndrome and its prevalence with modern lifestyle is increasing incessantly. Chronic hyperglycemia can induce several vascular complications that were referred to be the major cause of morbidity and mortality in DM. Although several therapeutic targets have been identified and accessed clinically, the imminent risk of DM and its prevalence are still ascending. Substantial pieces of evidence revealed that histone deacetylase (HDAC) isoforms can regulate various molecular activities in DM via epigenetic and post-translational regulation of several transcription factors. To date, 18 HDAC isoforms have been identified in mammals that were categorized into 4 different classes. Classes I, II, and IV are regarded as classical HDACs, which operate through a Zn-based mechanism. In contrast, class III HDACs or Sirtuins depend on nicotinamide adenine dinucleotide (NAD+) for their molecular activity. Functionally, most of the HDAC isoforms can regulate β cell fate, insulin release, insulin expression and signaling, and glucose metabolism. Moreover, the roles of HDAC members have been implicated in the regulation of oxidative stress, inflammation, apoptosis, fibrosis, and other pathological events, which substantially contribute to diabetes-related vascular dysfunctions. Therefore, HDACs could serve as the potential therapeutic target in DM towards developing novel intervention strategies. This review sheds light on the emerging role of HDACs/isoforms in diabetic pathophysiology and emphasized the scope of their targeting in DM for constituting the novel interventional strategies for metabolic disorders/complications.

The nuclear factor-erythroid 2 p45-related factor 2 (Nrf2, also called Nfe2l2)/Kelchlike ECH-associated protein 1 (Keap1) signaling is the major regulator of redox homeostasis. The imbalance of redox homeostasis causes oxidative stress. Keap1 is the one that regulates Nrf2 by binding to Nrf2. Nrf2/Keap1 signaling is reported to be involved in cancer cell growth and survival. The high level of Nrf2 in cancers is associated with poor prognosis, resistance to therapeutics and rapid proliferation framing Nrf2 as an interesting target in cancer biology. Sirtuins (SIRT1-7) are class III histone deacetylases with NAD+-dependent deacetylase activity. High levels of SIRT6 are contributing to cancer progression in many types of human tumors, and its overexpression has been reported to involve positive modulation of the Nrf2/Keap1 pathway, suggesting SIRT6 is a key regulator of this Nrf2/Keap1 Signaling. The natural or synthetic compound that inhibits key regulators of Nrf2 signaling becomes an attractive target. In the present study, we investigated the pharmacological effect of Ethyl (5-(4-Chlorophenyl)-2-methyl-1H-imidazol-4-yl) - acetate an imidazole derivative on Nrf2/Keap1 in A549 and NIC-H460 cell lines. Imidazole derivative inhibited the SIRT6 expression at gene and protein levels. The gene and protein expression of Nrf2 and Keap1 were modulated during SIRT6 inhibition. The level of anti-oxidant enzymes such as GSH, GPx, Catalase, and % ROS scavenging activity were depleted upon SIRT6 inhibition. Further, morphological studies support ROS generation, mitochondrial damage, nuclear damage, and apoptosis. The molecular examination of apoptosis by gene and protein expression of apoptotic factors confirms apoptotic cell death. Our results suggest that the Imidazole derivative affects Nrf2/Keap1 signaling by targeting SIRT6 might be a new promising approach to cancer treatment opportunity for disrupting Nrf2/Keap1 signaling in lung cancer.