Phytochemicals and Cancer Chemoprevention: Epigenetic Friends or Foe?

Cancer, as one of the non-communicable diseases, remains one of the leading causes of death around the world. Since immune cells that infiltrate tumors engage in an extensive and dynamic crosstalk with cancer cells, inflammatory responses play decisive roles at different stages of tumor development, including initiation, promotion, malignant conversion, invasion, and metastasis. Inflammation also affects immune surveillance and therapy sensitivity. Recent successes of therapeutic interventions in cancer and inflammatory diseases using epigenetic modifiers such as histone deacetylase inhibitors and inhibitors of DNA methylation suggest that epigenetic reprogramming plays an important role in the aetiology of these diseases. Epigenetic changes in DNA methylation patterns at CpG sites (epimutations) or corrupt chromatin states of tumor promoting genes and noncoding RNAs, recently emerged as major governing factors in tumor progression and cancer drug sensitivity. Epigenetic defects (epimutations) are thought to be more easily reversible (when compared with genetic defects) and, as such, have inspired efforts to identify novel compounds that correct epimutations or prevent disease progression. Given the fact that epigenetic modifications occur early in carcinogenesis and represent potentially initiating events in cancer development, they have been identified as promising new targets for chemoprevention strategies. Numerous clinical, epidemiological and laboratory studies have identified various promising nutritional anti-inflammatory compounds as chemopreventive agents, which affect carcinogenic epigenetic marks in the body and the host immune system, and protect against aggressive cancer malignancies. This has recently launched reexploration of chemopreventive phytochemicals for identification of epigenetic targets which allow epigenetic (re)programming of cancer stem cells, prevent metastasis or sensitize for drug sensitivity. This review will discuss mechanisms of epigenome plasticity by cancer-inflammation and chemopreventive phytochemicals

Molecular insight in the multifunctional activities of Withaferin A

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Dietary curcumin inhibits atherosclerosis by affecting the expression of genes involved in leukocyte adhesion and transendothelial migration

International audienceScope The aim of the study was to examine the atheroprotective effect of dietary curcumin in a mouse model of atherosclerosis and to identify its cellular and molecular targets at the vascular level. Methods and results ApoE/ mice were fed with curcumin at 0.2% (wt/wt) in diet for 4 months. This supplementation reduced the extent of atherosclerotic lesion by 26% and induced changes in expression of genes implicated in cell adhesion and transendothelial migration or cytoskeleton organization, as revealed by a transcriptomic analysis in the aorta. Expression profile of these genes suggests reduction in both leukocyte adhesion and transendothelial migration. In agreement with this hypothesis, we observed a reduction (37%) in macrophage infiltration in the plaque, as measured by immunohistochemistry, and, in vitro, a lower adhesion of monocytes to TNF-a-stimulated endothelial cells (32%) after exposure to a nutritionally achievable concentration of curcumin. These changes in gene expression could be related to the observed increased expression of I?B protein and decrease of TNF-a-induced NF-?B/DNA binding and NF-?B-transcriptional activity upon exposure to curcumin. Conclusion Our findings pointed out that the antiatherogenic effect of curcumin could be linked to its effect on gene networks and cell functions related to leukocyte adhesion and transendothelial migration via NF-?B-dependent pathways