Can beta-carotene regulate cell growth by a redox mechanism? An answer from cultured cells.

Many studies suggest a protective role of beta-carotene against cancer. However, the ATBC and the CARET trials have shown that beta-carotene increases the incidence of lung cancer in heavy smokers and asbestos workers. To explain this paradox, it can be hypothesized that beta-carotene modulates intracellular redox status and through this mechanism, it affects redox-sensitive molecular pathways involved in the regulation of cell cycle progression and apoptosis. Studies conducted in cultured cells seem to confirm such a hypothesis. At low concentrations, the carotenoid may serve as an antioxidant, inhibiting free radical production, while at relatively high concentrations and/or in the presence of a chronic oxidative stress (i.e. smoke), it may behave as a prooxidant, propagating free radical-induced reactions, consuming endogenous antioxidants and inducing DNA oxidative damage. In this context, it may regulate cell growth and death by the modulation of redox-sensitive genes and transcription factors.