A high degree of developmental plasticity enables plants to adapt to continuous, often unfavorable and unpredictable changes in their environment. At the molecular level, adaptive advantages for plants are primarily provided by epigenetic machinery including DNA methylation, histone modifications, and the activity of noncoding RNA molecules. Using a mass spectrometry-based proteomic approach, we examined the levels of acetylated histone peptide forms in Arabidopsis plants with a loss of function of histone deacetylase 6 (HDA6), and in plants germinated in the presence of HDA inhibitors trichostatin A (TSA) and sodium butyrate (NaB). Our analyses revealed particular lysine sites at histone sequences targeted by the HDA6 enzyme, and by TSA- and NaB-sensitive HDAs. Compared with plants exposed to drugs, more dramatic changes in the overall profiles of histone post-translational modifications were identified in hda6 mutants. However, loss of HDA6 was not sufficient by itself to induce hyperacetylation to the maximum degree, implying complementary activities of other HDAs. In contrast to hda6 mutants that did not exhibit any obvious phenotypic defects, the phenotypes of seedlings exposed to HDA inhibitors were markedly affected, showing that the effect of these drugs on early plant development is not limited to the modulation of histone acetylation levels.

• Klíčová slova
• Arabidopsis thaliana, epigenetics, histone, mass spectrometry, post-translational modifications, sodium butyrate, trichostatin A,
• MeSH
• Arabidopsis genetika   růst a vývoj   MeSH
• histondeacetylasy genetika   MeSH
• histonový kód účinky léků   genetika   MeSH
• inhibitory histondeacetylas farmakologie   MeSH
• klíčení genetika   MeSH
• kyselina máselná farmakologie   MeSH
• kyseliny hydroxamové farmakologie   MeSH
• metylace DNA účinky léků   MeSH
• proteiny huseníčku antagonisté a inhibitory   genetika   MeSH
• proteomika * MeSH
• regulace genové exprese u rostlin MeSH
• semenáček účinky léků   genetika   MeSH
• umlčování genů MeSH
• vývoj rostlin účinky léků   genetika   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• AT5G63110 protein, Arabidopsis MeSH Prohlížeč
• histondeacetylasy MeSH
• inhibitory histondeacetylas MeSH
• kyselina máselná MeSH
• kyseliny hydroxamové MeSH
• proteiny huseníčku MeSH
• trichostatin A MeSH Prohlížeč

Carcinogenesis cannot be explained only by genetic alterations, but also involves epigenetic processes. Modification of histones by acetylation plays a key role in epigenetic regulation of gene expression and is controlled by the balance between histone deacetylases (HDAC) and histone acetyltransferases (HAT). HDAC inhibitors induce cancer cell cycle arrest, differentiation and cell death, reduce angiogenesis and modulate immune response. Mechanisms of anticancer effects of HDAC inhibitors are not uniform; they may be different and depend on the cancer type, HDAC inhibitors, doses, etc. HDAC inhibitors seem to be promising anti-cancer drugs particularly in the combination with other anti-cancer drugs and/or radiotherapy. HDAC inhibitors vorinostat, romidepsin and belinostat have been approved for some T-cell lymphoma and panobinostat for multiple myeloma. Other HDAC inhibitors are in clinical trials for the treatment of hematological and solid malignancies. The results of such studies are promising but further larger studies are needed. Because of the reversibility of epigenetic changes during cancer development, the potency of epigenetic therapies seems to be of great importance. Here, we summarize the data on different classes of HDAC inhibitors, mechanisms of their actions and discuss novel results of preclinical and clinical studies, including the combination with other therapeutic modalities.

• Klíčová slova
• anti-angiogenic effect, apoptosis, autophagy, cancer, cell cycle arrest, drug combinations, histone deacetylase inhibitors, histone deacetylases,
• MeSH
• acetylace účinky léků   MeSH
• apoptóza účinky léků   MeSH
• autofagie účinky léků   MeSH
• epigeneze genetická účinky léků   MeSH
• imunomodulace účinky léků   MeSH
• inhibitory angiogeneze farmakologie   terapeutické užití   MeSH
• inhibitory histondeacetylas farmakologie   terapeutické užití   MeSH
• klinické zkoušky jako téma MeSH
• kontrolní body buněčného cyklu účinky léků   MeSH
• lidé MeSH
• preklinické hodnocení léčiv MeSH
• protinádorové látky farmakologie   terapeutické užití   MeSH
• protokoly protinádorové kombinované chemoterapie škodlivé účinky   terapeutické užití   MeSH
• regulace genové exprese u nádorů účinky léků   MeSH
• signální transdukce účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• inhibitory angiogeneze MeSH
• inhibitory histondeacetylas MeSH
• protinádorové látky MeSH