title: Curcumin induces senescence of primary human cells building the vasculature in a DNA damage and ATM-independent manner.
abstract: Curcumin is considered not only as a supplement of the diet but also as a drug in many types of diseases and even as a potential anti-aging compound. It can reduce inflammation that increases with age and accompanies almost all age-related diseases. It has been suggested that curcumin can play a beneficial role in the cardiovascular system. However, there are also data showing that curcumin can induce senescence in cancer cells, which is a beneficial effect in cancer therapy but an undesirable one in the case of normal cells. It is believed that cellular senescence accompanies age-related changes in the cardiovascular system. The aim of this study was to check if curcumin, in a certain range of concentrations, can induce senescence in cells building the vasculature. We have found that human vascular smooth muscle and endothelial cells derived from aorta are very sensitive to curcumin treatment and can senesce upon treatment with cytostatic doses. We observed characteristic senescence markers but the number of DNA damage foci decreased. Surprisingly, in vascular smooth muscle cell (VSMC) activation of DNA damage response pathway downstream of ataxia-telangiectasia mutated (ATM) was observed. ATM silencing and the supplementation of antioxidants, N-acetyl-L-cysteine (NAC) or trolox, did not reduce the number of senescent cells. Thus, we have shown that curcumin can induce senescence of cells building the vasculature, which is DNA damage and ATM independent and is not induced by increased reactive oxygen species (ROS) level. We postulate that an increase in the bioavailability of curcumin should be introduced very carefully considering senescence induction as a side effect.
authors: Department of Biochemistry, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Pasteur Str. 3, 02-093, Warsaw, Poland.
authors: Wioleta
authors: W
authors: Grabowska
authors: Karolina
authors: K
authors: Kucharewicz
authors: Maciej
authors: M
authors: Wnuk
authors: Anna
authors: A
authors: Lewinska
authors: Małgorzata
authors: M
authors: Suszek
authors: Dorota
authors: D
authors: Przybylska
authors: Grazyna
authors: G
authors: Mosieniak
authors: Ewa
authors: E
authors: Sikora
authors: Anna
authors: A
authors: Bielak-Zmijewska
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects / Q000473:pathology; D064007:Ataxia Telangiectasia Mutated Proteins; D018929:Cell Culture Techniques; D049109:Cell Proliferation / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects*; D003474:Curcumin / Q000494:pharmacology*; D004249:DNA Damage; D042783:Endothelial Cells / Q000187:drug effects*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D064007:Ataxia Telangiectasia Mutated Proteins; D003474:Curcumin
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