title: Curcumin induces oxidation-dependent cell cycle arrest mediated by SIRT7 inhibition of rDNA transcription in human aortic smooth muscle cells.
abstract: It is widely accepted that abnormal accumulation of vascular smooth muscle cells (VSMCs) may promote atherosclerosis and post-angioplasty restenosis. The use of some plant polyphenols with potent antiproliferative activities may be considered as a therapeutic intervention to diminish/prevent the development of cardiovascular pathologies. In the present study, VSMC response to curcumin treatment was evaluated. 5 μM curcumin elicited a cytostatic effect, which was accompanied by protein carbonylation, oxidative DNA damage and changes in the nucleolar activity (the size and number of nucleoli, nucleolar protein levels and their localization). The levels of p53 and p21 were elevated. However, this was independent of DNA DSBs. Curcumin caused inhibition of rDNA transcription, which could be due to SIRT7 downregulation, site-specific methylation of RNA18S5 gene promoter or both. Curcumin-induced DNA methyltransferase 2 (DNMT2) upregulation was also shown. DNMT2-mediated RNA methylation could promote RNA stabilization upon curcumin treatment. In conclusion, a nucleolus-focused cytostatic action of curcumin at a low micromolar concentration range, which could be feasibly achieved through dietary means, was established in VSMCs and we propose a novel mechanism underlying this action. We believe that our results may contribute to better understanding of the biological and pharmacological effects of curcumin on the human cardiovascular system.
authors: Department of Biochemistry and Cell Biology, University of Rzeszow, Rzeszow, Poland. Electronic address: alewinska@o2.pl.
authors: Anna
authors: A
authors: Lewinska
authors: Department of Genetics, University of Rzeszow, Rzeszow, Poland.
authors: Maciej
authors: M
authors: Wnuk
authors: Laboratory of Molecular Bases of Aging, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland.
authors: Wioleta
authors: W
authors: Grabowska
authors: Laboratory of Genomics, National Research Institute of Animal Production, Balice n. Cracow, Poland.
authors: Tomasz
authors: T
authors: Zabek
authors: Laboratory of Genomics, National Research Institute of Animal Production, Balice n. Cracow, Poland.
authors: Ewelina
authors: E
authors: Semik
authors: Laboratory of Molecular Bases of Aging, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland.
authors: Ewa
authors: E
authors: Sikora
authors: Laboratory of Molecular Bases of Aging, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland. Electronic address: anb@nencki.gov.pl.
authors: Anna
authors: A
authors: Bielak-Zmijewska
mesh_terms: D001011:Aorta / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D002466:Cell Nucleolus / Q000187:drug effects; D002478:Cells, Cultured; D003474:Curcumin / Q000494:pharmacology*; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000032:analysis; D019175:DNA Methylation; D004275:DNA, Ribosomal / Q000235:genetics*; D006801:Humans; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000378:metabolism; D037761:Sirtuins / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D004275:DNA, Ribosomal; D011506:Proteins; C510661:SIRT7 protein, human; D004248:DNA (Cytosine-5-)-Methyltransferases; C112218:TRDMT1 protein, human; D037761:Sirtuins; D003474:Curcumin
keywords: Curcumin; DNMT2; Nucleolus; SIRT7; VSMCs; rDNA