Lycopene's Chemoprotective Mechanism Against Breast Cancer

Researchers in Hong Kong, People's Republic of China, have uncovered the chemoprotective mechanism by which lycopene prevents polycyclic aromatic hydrocarbons (PAH)-induced carcinogenesis in the breast. Lycopene, a carotenoid widely distributed in fruit and vegetables, has been shown to inhibit phase 1 enzymes and induce phase 2 enzymes, facilitating the elimination of genotoxic moieties and reducing cancer risk. The study, published in the journal Nutrition, demonstrated that lycopene's inhibitory action on cytochrome P450 1A1 and 1B1 enzymes and its induction of uridine diphosphate-glucuronosyltransferases (UGT) were the underlying protective mechanisms against PAH-induced toxicity.

Key Takeaways:

• Lycopene, a carotenoid found in fruit and vegetables, has been associated with decreased cancer risk in epidemiological studies.
• Animal studies have shown that lycopene may protect against dimethylbenz[a]anthracene (DMBA)-induced carcinogenesis in the breast.
• Lycopene's chemoprotective mechanism involves inhibiting phase 1 enzymes, such as cytochrome P450 1A1 and 1B1, and inducing phase 2 enzymes, such as UDP-glucuronosyltransferases (UGT).
• The study used a cell culture model, MCF-7, to investigate the mechanism of lycopene's protective effect against PAH-induced carcinogenesis.
• Lycopene inhibited recombinant CYP1A1 and CYP1B1 enzymes with estimated K(i)s in the micromolar range.
• In MCF-7 cells, lycopene administration reduced DMBA-induced ethoxyresorufin-O-deethylase activity by 20%.
• A four-fold increase in microsomal UGT activity was observed in response to lycopene administration.

Statistics:

• Lycopene's inhibitory action on CYP1 enzymes was assessed in recombinant protein and cell culture using ethoxyresorufin-O-deethylase assay.
• The study demonstrated a 20% reduction in DMBA-induced ethoxyresorufin-O-deethylase activity in response to lycopene administration.
• A four-fold increase in microsomal UGT activity was observed following lycopene administration.
• The chemoprotective mechanism of lycopene involved a K(i) of 4.5 ± 0.5 μM for CYP1A1 and 5.3 ± 0.6 μM for CYP1B1.

Sources:

• Wang, H. A., et al. (2010). The carotenoid lycopene differentially regulates phase I and II enzymes in dimethylbenz[a]anthracene-induced MCF-7 cells. Nutrition, 26(11-12), 1181-1187.
• Gene Therapy Weekly editors. (2010). Lycopene's Chemoprotective Mechanism Against Breast Cancer. Gene Therapy Weekly via NewsRx.com.