Inducers of Senescence, Toxic Compounds, and Senolytics: The Multiple Faces of Nrf2-Activating Phytochemicals in Cancer Adjuvant Therapy

Figure 2

Potential mechanisms leading to senescence by NRF2-activating compounds in cancer cells. The response under NRF2 signaling involve the activation of glutamylcysteine ligase (γ-GCL), glutathione peroxidase (GPx), heme oxygenase 1 (HO-1), superoxide dismutase (SOD), glutathione S-transferase (GST), and many other enzymes involved in the antioxidant cytoprotective response that lead to suppression of senescence-related pathways (i.e., p53, p21, and p16). However, this response include and interact with additional genes, such as Notch-1, NADPH-quinone oxidoreductase (NQO1), the aryl hydrocarbon receptor (AhR), the Jun dimerization protein 2 (JDP2), and perhaps epigenetic changes that may be involved in sensing stress and damage and that are known to participate in processes leading to cellular senescence. In the case of (particular) cancer cells, the persistence of unresolved damage can eventually lead these pathways to the reactivation of the senescence program.