A Novel Combination of Withaferin A and Sulforaphane Inhibits Epigenetic Machinery, Cellular Viability and Induces Apoptosis of Breast Cancer Cells

With cancer often classified as a disease that has an important epigenetic component, natural compounds that have the ability to regulate the epigenome become ideal candidates for study. Humans have a complex diet, which illustrates the need to elucidate the mechanisms of interaction between these bioactive compounds in combination. The natural compounds withaferin A (WA), from the Indian winter cherry, and sulforaphane (SFN), from cruciferous vegetables, have numerous anti-cancer effects and some report their ability to regulate epigenetic processes. Our study is the first to investigate the combinatorial effects of low physiologically achievable concentrations of WA and SFN on breast cancer cell proliferation, histone deacetylase1 (HDAC1) and DNA methyltransferases (DNMTs). No adverse effects were observed on control cells at optimal concentrations. There was synergistic inhibition of cellular viability in MCF-7 cells and a greater induction of apoptosis with the combinatorial approach than with either compound administered alone in both MDA-MB-231 and MCF-7 cells. HDAC expression was down-regulated at multiple levels. Lastly, we determined the combined effects of these bioactive compounds on the pro-apoptotic BAX and anti-apoptotic BCL-2 and found decreases in BCL-2 and increases in BAX. Taken together, our findings demonstrate the ability of low concentrations of combinatorial WA and SFN to promote cancer cell death and regulate key epigenetic modifiers in human breast cancer cells

Coronal leakage of provisional restorative materials used in endodontics with and without intracanal medication after exposure to human saliva

Aim: To determine the coronal leakage of various provisional restorations with and without intracanal medication over time after being exposed to human saliva. Materials and Methods: This study investigated Coltosol F, Cavit, Ketac Molar, and IRM as provisional restorative material. Calcium hydroxide and chlorhexidine were used as an intracanal medicament. Ninety-eight single rooted teeth were randomly selected and then mounted in an apparatus that isolated the crown portion of the tooth. Provisional restorative materials were placed in the access cavity following manufacturer guidelines after placement of intracanal medicament. Human saliva and brain heart infusion broth in 3:1 ratio were applied to the samples, incubated at 37°C, and results were tabulated over the course of 4 weeks by the appearance of turbidity in the lower part of the apparatus. Statistical Analysis: The data were statistically analyzed using proportional Z-test. The level of significance was set at 0.05. Results: Coltosol F and Cavit could significantly prevent the bacterial leakage up to a period of 7 days with a P value of 0.01 and 0.005, respectively. Bacterial recontamination was relatively less in the samples treated with intracanal medicaments up to 14 days. After 14 days, however, all materials leaked in over half of the samples. Conclusion: No provisional restorative material can be considered superior in providing a reliable seal after 14 days. Inter-appointments schedule should not extend beyond 2 weeks and after endodontic therapy final restoration should be completed within 1 week

Epigenetic Regulation of Epidermal Stem Cell Biomarkers and Their Role in Wound Healing

As an actively renewable tissue, changes in skin architecture are subjected to the regulation of stem cells that maintain the population of cells responsible for the formation of epidermal layers. Stems cells retain their self-renewal property and express biomarkers that are unique to this population. However, differential regulation of the biomarkers can initiate the pathway of terminal cell differentiation. Although, pockets of non-clarity in stem cell maintenance and differentiation in skin still exist, the influence of epigenetics in epidermal stem cell functions and differentiation in skin homeostasis and wound healing is clearly evident. The focus of this review is to discuss the epigenetic regulation of confirmed and probable epidermal stem cell biomarkers in epidermal stratification of normal skin and in diseased states. The role of epigenetics in wound healing, especially in diseased states of diabetes and cancer, will also be conveyed