Sirtuins as a double-edged sword in cancer: From molecular mechanisms to therapeutic opportunities

Abstract

Sirtuins are a family of NAD + -dependent enzymes that participate in cellular adaptation to stress, particularly to stress associated with changes in energy metabolism. Sirtuins originated in prokaryotes, participating in vitamin-B12 metabolism, and later appeared in early eukaryotes with an additional function: protecting the genome from endogenous or exogenous stress. This early origin places Sirtuins at the intersection of various stress-related pathways within the complex signaling network that regulates stress response. Thus, Sirtuins are critical in many human pathologies—especially cancer and aging. In cancer, Sirtuins can act as tumor promoters or suppressors, depending on the cell type and the functional context. Therefore, they are promising targets for cancer therapeutics and, according to some evidence, might serve as biomarkers of tumor status and stage.