Figure 2.

The role of quercetin in the metabolism of ROS in cancer cells. Reactive oxygen species (ROS) are continuously generated in cancer cells as a result of several factors, including increased metabolic activity, the activation of oncogenes, and the eventual loss of p53. The increase of ROS plays an important role in the maintenance of cancer phenotype and leads to a condition of pro-oxidative state. In turn, ROS can determine chromosomal instability (accumulation of mutations and deletions), and can stimulate cell growth and proliferation, as well as cell migration and invasiveness (angiogenesis and metastasis). The adaptation of cancer cells to this setting essentially involves the rearrangement of the antioxidant functions and the upregulation of pro-survival proteins. These changes allow them to bypass the cell death caused by excessive levels of ROS. The exposure to Quercetin (Qu) leads to the formations of quercetin-semiquinones and quercetin-quinones, which exert pro-oxidant effects within the cells. These compounds are highly reactive towards thiols and react with reduced glutathione (GSH), causing GSH depletion. The disruption of GSH antioxidant defense in cells with persistent ROS overload, like malignant cells, leads to cell death by apoptosis. LPO, lactic peroxidase; O₂⁻, superoxide anion; H₂O₂, hydrogen peroxide; GSH, glutathione; GS•, oxidized GSH; GSSG, glutathione disulfide.