Biological activity of lycopene metabolites: implications for cancer prevention

Abstract

While early studies focused on the potential roles in health and disease of provitamin A carotenoids, such as beta-carotene, research over the past decade has provided a framework for our understanding of the functions of non-provitamin A carotenoids such as lycopene, especially in regards to its association with a reduced risk of a number of chronic diseases, including cancer. Recent data suggests that lycopene metabolites may possess specific biological activities on several important cellular signaling pathways and molecular targets. Carotenoid metabolites may have more important biological roles than their parent compounds in human health and disease. This notion has been reinforced by the observation of both beneficial and detrimental effects of carotenoid metabolites in cancer prevention.

Figure 1. Possible biological functions of lycopene.

Figure 2. Metabolic pathway of β-carotene, and chemical structures of provitamin A carotenoids (β-carotene, α-carotene, and β-cryptoxanthin) and non-provitamin A carotenoids (lutein, zeaxanthin, and lycopene).

Adapted from Merntiz et al. (2007).

Figure 3. Schematic illustration of lycopene metabolic pathway by CMO2.

(A) 5-cis and 13-cis lycopene are preferentially cleaved by CMO2 at 9′10′-double bond. The cleavage product, apo-10′-lycopenal, can be further oxidized to apo-10′-lycopenol or reduced to apo-10′-lycopenoic acid, dependent on the presence of NADH. (B) Chemical structures of apo-10′-lycopenoic acid, acycloretinoic acid, and all-trans retinoic acid. Adapted from Hu et al. (2006).

Figure 4. The involvement of RARE on apo-10′-lycopenoic acid-transactivated RARβ expression.

Upper panel shows a diagram of the construction of the RARβ reporter vector with wild-type or mutated RARE. Lower panel, RARβ reporter vector was treated with apo-10′-lycopenoic acid or all-trans retinoic acid for 24 h. Luciferase activities were measured by dual-luciferase reporter system. Values are means ± SEM of three replicate assays. *Statistically different, as compared with control in the same group, P < 0.05. Adapted from Lian et al. (2007).

Figure 5. Effect of apo-10’-lycopenoic acid, apo10’-lycopenol, and apo-10’-lycopenal on hemooxygenase-1 gene expression.

Values are means ± SEM of three replicate assays. Adapted from Lian et al. (2008).

Figure 6. Effect of apo-10′-lycopenoic acid supplementation on NNK-induced lung tumor development in A/J mice.

A/J mice were fed control diet or diet supplemented with apo-10′-lycopenoic acid for 16 weeks. Lung tumors were induced by injection of NNK at week 3 of supplementation. Tumor nodules on the surface of mouse lung tissues were counted and recorded as tumor multiplicity (tumors/mouse). Abbreviations: CNTL, non-supplementation plus sham injection; NNK, non-supplementation plus NNK injection; LYA10, LYA40, and LYA120, 10, 40, and 120 mg/kg diet of apo-10′lycopenoic acid supplementation plus NNK injection. Values are presented as means ± SEM, n = 12–14. Groups that do not share a letter are significantly different, P < 0.05. Adapted from Lian et al. (2007).