ABSTRACT
Evidence has accumulated from many prospective as well as retrospective
epidemiological studies that individuals eating more fruits and vegetables rich in
carotenoids (1), or having higher blood concentrations of carotenoids (2), decrease
their risk for developing cancer, especially lung cancer. In contrast, the role of
carotenoids in the prevention of cancer has been brought into question by the
results of several intervention trials. These studies not only failed to detect any
protective effect of b-carotene or of a combination of b-carotene and vitamin A on the incidence of diverse cancers, but two of them [the b-Carotene and Retinol Efficacy Trial (CARET; 3) and the Alpha-Tocopherol, Beta-Carotene Cancer
Prevention Study (ATBC, 4)] even show that these compounds can increase the
incidence of lung cancer. Although these unexpectedly adverse effects have been
obtained in populations at risk for lung cancer (smokers, ex-smokers, or asbestos
workers) and the supplemented b-carotene has been given at a stage where the cancers were most likely already in the later phase (progression), there is concern
that most of the clinical trials giving b-carotene as a supplement have been stopped. A great deal of emphasis has been given to the understanding of the
mechanism(s) of action by which carotenoids may modulate physiological
functions and influence the progression of chronic diseases, inducing beneficial or
adverse health effects. A possible mechanism that can explain the dual role of
carotenoid molecules as both beneficial and harmful agents in cancer as well as in
other chronic diseases is their ability to modulate intracellular redox status.
Carotenoid molecules may serve as antioxidants (5-7), inhibiting free radical
production, or as pro-oxidants (8-10), propagating free radical-induced reactions,
depending on their intrinsic properties as well as on the redox potential of the
biological environment in which they act. In other words, these compounds may
behave as reactants in a continuity of electron-donating and accepting agents
commonly found in cells (11). In this context, their antioxidant function may not be
inherently good, and their pro-oxidant activity may not necessarily be bad. This
review summarizes the available evidence for a pro-oxidant activity of carotenoids
in vitro and in vivo. In particular, it focuses on (a) the main factors influencing the
pro-oxidant activity of carotenoids, (b) the biological and molecular targets
evidencing such an activity, and (c) the possible implications of carotenoid
oxidative functions in health and disease.
