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

Figure 1

Potential effects and concerns of selected natural compounds as adjuvant in cancer therapy. Based on experiments “in vitro,” epigallocatechin gallate (EGCG), tocotrienols, curcumin, quercetin, genistein, resveratrol, silybin, phenyl isothiocyanate (PEITC), sulforaphane, triptolide, allicin, berberine, piperlongumine, fisetin, phloretin might be useful in prevention and therapy of cancer. Gero- and cancer preventive activity include (1) induction senescence or apoptosis in normal damaged and potentially precancerous cells, (2) protection of normal cells by damage via modulation of antioxidant/cytoprotective pathways, and (3) anti-inflammatory activity that might reduce negative effects of the senescence-associated secretory phenotype (SASP) produced by senescent cells. In cancer therapy, natural bioactive compound might help (4) to induce apoptosis and senescence in cancer cells thus helping to reduce dosage of chemo- and radiotherapy while keeping efficacy. The major concern regards the possibility that these compounds might act as cytoprotective in some cancer cells (as in normal cells), thus aggravating the problem of resistance of cancer to therapy (5). However, failure to clearance senescent cells (6), as it might occur in immune-compromised subjects, might represent a serious challenge for these applications. Inclusion of additional strategies (7) with other natural compounds (i.e., phloretin, fisetin, piperlongumine, and quercetin) able to induce selective death of senescent cells should be evaluated in future preclinical studies to reduce relapses and side effects of chemo- or radiotherapy.