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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.
This article was published in the following journal.
Name: International journal of molecular sciences
Epigenetic modification is an additional regulator in immune responses as the genome-wide profiling somehow fails to explain the sophisticated mechanisms in autoimmune diseases. The effect of epigenet...
Ischemia/reperfusion (I/R) injury has been correlated with systemic inflammatory response. In addition, NLRP3 has been suggested as a cause in many inflammatory processes. Sulforaphane (SFN) is a natu...
Small molecule drugs and probes are important tools in drug discovery, pharmacology, and cell biology. This is of course also true for epigenetic inhibitors. Important examples for the use of establis...
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Viruses are important human and animal pathogens causing disease that affect global health and the economy. One outcome of many virus infections is the regulation of cellular trafficking machinery. Vi...
The goal of the study is to investigate whether adding different doses of sulforaphane will benefit the clinical symptoms and cognitive function in individuals who have schizophrenia. Thi...
This research study involves taking an experimental anti-cancer dietary supplement called Sulforaphane (SF) or a placebo (product without any supplement content) over a period of twelve mo...
The aim of this randomized controlled trial is to determine if a nutritional supplement containing broccoli sprout and seed extracts, a rich source of sulforaphane, is effective in reducin...
In this proposed study, the investigators will evaluate the the efficacy, safety and related mechanism of sulforaphane in treatment of autism spectrum disorder (ASD). The study will recrui...
This is an open-label, 4-month study examining the effects of Sulforaphane (SF) on behavior in children with ASD and the correlation between behavior change and urinary metabolites. The go...
A cytotoxic sulfhydryl reagent that inhibits several subcellular metabolic systems and is used as a tool in cellular physiology.
The systematic study of the global gene expression changes due to EPIGENETIC PROCESSES and not due to DNA base sequence changes.
Antifungal metabolite from several fungi, mainly Trichoderma viride; inhibits protein synthesis by binding to ribosomes; proposed as antifungal and antineoplastic; used as tool in cellular biochemistry.
An antibiotic substance produced by Streptomyces species. It inhibits mitochondrial respiration and may deplete cellular levels of ATP. Antimycin A1 has been used as a fungicide, insecticide, and miticide. (From Merck Index, 12th ed)
An Ig domain-containing membrane receptor that is expressed by TH1 CELLS. It regulates the activation of MACROPHAGES and inhibits TH1-mediated auto- and alloimmune responses to promote IMMUNE TOLERANCE.
The development and maintenance of an organism is orchestrated by a set of chemical reactions that switch parts of the genome off and on at strategic times and locations. Epigenetics is the study of these reactions and the factors that influence them. ...