Abstract
Emerging evidence suggests that Sirtuin 6 (SIRT6) functions as a longevity assurance gene by promoting genomic stability, regulating metabolic processes and attenuating inflammation. Here, we examine the effect of SIRT6 activation on cancer cells. We show that SIRT6 overexpression induces massive apoptosis in a variety of cancer cell lines but not in normal, non-transformed cells. This cell death requires the mono-ADP-ribosyltransferase but not the deacetylase activity of SIRT6 and is mediated by the activation of both the p53 and p73 apoptotic signaling cascades in cancer cells by SIRT6. These results suggest that SIRT6 is an attractive target for pharmacological activation in cancer treatment.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
ADP Ribose Transferases / genetics
-
ADP Ribose Transferases / metabolism
-
Apoptosis*
-
Cell Line, Tumor
-
Cell Survival
-
Culture Media / chemistry
-
DNA-Binding Proteins / genetics
-
DNA-Binding Proteins / metabolism
-
Gene Expression Regulation, Neoplastic*
-
Glucose / metabolism
-
Humans
-
Mutagenesis, Site-Directed
-
Nuclear Proteins / genetics
-
Nuclear Proteins / metabolism
-
Phenanthrenes / pharmacology
-
Plasmids / genetics
-
Plasmids / metabolism
-
Poly (ADP-Ribose) Polymerase-1
-
Poly(ADP-ribose) Polymerase Inhibitors
-
Poly(ADP-ribose) Polymerases / metabolism
-
Signal Transduction
-
Sirtuins / genetics
-
Sirtuins / metabolism*
-
Transfection
-
Transgenes
-
Tumor Protein p73
-
Tumor Suppressor Protein p53 / genetics
-
Tumor Suppressor Protein p53 / metabolism
-
Tumor Suppressor Proteins / genetics
-
Tumor Suppressor Proteins / metabolism
Substances
-
Culture Media
-
DNA-Binding Proteins
-
N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride
-
Nuclear Proteins
-
Phenanthrenes
-
Poly(ADP-ribose) Polymerase Inhibitors
-
TP53 protein, human
-
TP73 protein, human
-
Tumor Protein p73
-
Tumor Suppressor Protein p53
-
Tumor Suppressor Proteins
-
ADP Ribose Transferases
-
PARP1 protein, human
-
Poly (ADP-Ribose) Polymerase-1
-
Poly(ADP-ribose) Polymerases
-
SIRT6 protein, human
-
Sirtuins
-
Glucose