text: Due to the regulatory role during transcription of epigenetic modifications in genes, it is not surprising that changes in epigenetic markers, such as acetylation, can contribute to cancer development. HDACs expression and activity in tumor cells is very different from normal cells. The overexpression and increased activity of HDACs has been shown to be characteristic of tumorigenesis and metastasis, suggesting an important regulatory role of histone deacetylation on the expression of tumor suppressor genes. One of the examples is the regulation role of histone acetylation/deacetylation in P300 and CBP, both of which contribute to oncogenesis.
  Approved in 2006 by the U.S. Food and Drug Administration (FDA), Vorinostat represents a new category for anticancer drugs that are in development. Vorinostat targets histone acetylation mechanisms and can effectively inhibit abnormal chromatin remodeling in cancerous cells. Targets of Vorinostat includes HDAC1, HDAC2, HDAC3 and HDAC6.
  Carbon source availability is reflected in histone acetylation in cancer. Glucose and glutamine are the major carbon sources of most mammalian cells, and glucose metabolism is closely related to histone acetylation and deacetylation. Glucose availability affects the intracellular pool of acetyl-CoA, a central metabolic intermediate that is also the acetyl donor in histone acetylation. Glucose is converted to acetyl-CoA by the pyruvate dehydrogenase complex (PDC), which produces acetyl-CoA from glucose-derived pyruvate; and by adenosine triphosphate-citrate lyase (ACLY), which generates acetyl-CoA from glucose-derived citrate. PDC and ACLY activity depend on glucose availability, which thereby influences histone acetylation and consequently modulates gene expression and cell cycle progression. Dysregulation of ACLY and PDC contributes to metabolic reprogramming and promotes the development of multiple cancers. At the same time, glucose metabolism maintains the NAD+/NADH ratio, and NAD+ participates in SIRT-mediated histone deacetylation. SIRT enzyme activity is altered in various malignancies, and inhibiting SIRT6, a histone deacetylase that acts on acetylated H3K9 and H3K56, promotes tumorigenesis. SIRT7, which deacetylates H3K18 and thereby represses transcription of target genes, is activated in cancer to stabilize cells in the transformed state. Nutrients appear to modulate SIRT activity. For example, long-chain fatty acids activate the deacetylase function of SIRT6, and this may affect histone acetylation.