Resumen
The role of autophagy and senescence in cancer resistance to ionizing radiation as a response to genotoxic stress is still only partially explored. The flavonoids quercetin and fisetin have previously been shown to sensitize cancer cells resistant to radiotherapy by targeting p16INK4 and p21Kip1. Here, we examined their ability to modulate autophagy and senescence-associated inflammatory markers after irradiation in radioresistant cells. Quercetin or fisetin, in association with ionizing radiation, significantly activated AMPK and decreased ERK kinase activity, which was linked to autophagic stress response and apoptosis induction. In simple words, on one side, the combined treatment favored the induction of autophagy and senescence by activating AMPK; on the other side, it lowered the threshold for cell death and induced lethal autophagy and apoptosis by inhibiting the ERK pathway.