Ascorbate-driven quinone redox cycling as a pro-oxidant anticancer strategy

Quinones are natural compounds widely distributed in animals, plants, and microorganisms, where they play essential roles in cellular energy metabolism. Ascorbate (vitamin C) can exert antioxidant or pro-oxidant effects depending on concentration and cellular context. Studies have shown that quinones can undergo redox cycling, leading to the generation of reactive oxygen species (ROS), a process that is further enhanced in the presence of ascorbate. Due to the elevated production of reactive oxygen species (ROS) and compromised antioxidant defenses in cancer cells, redox imbalance has been proposed as a potential "Achilles' heel" of tumors. In this context, the combination of ascorbate and quinones represents a promising strategy for selectively targeting cancer cells through enhanced ROS generation. This review discusses the mechanisms and biological effects of natural and synthetic quinoid compounds, particularly their interactions with ascorbate in cancer cells.