- Press release
, François-Xavier Branthôme
Tomatoes protect against development of UV-induced keratinocyte carcinoma via metabolomic alterations
Prolonged tomato consumption can mitigate ultraviolet (UV) light induced sunburn via unknown mechanisms. Dietary carotenoids distributed to skin are hypothesized to protect skin against UV-induced damage, although other phytochemicals may play a role. We hypothesize that tomato consumption would protect against skin cancer.
SKH-1 hairless and immunocompetent mice (n = 180) were fed AIN-93G or AIN-93G + 10% tangerine or red tomato powder for 35 weeks. From weeks 11–20, mice (n = 120) were exposed to 2240 J/m2 UV-B light, three times a week, and tumors were tracked weekly. Control mice were fed the same diets but not exposed to UV. Tumor number was significantly lower in male mice consuming red tomato diets (1.73 ± 0.50, P = 0.015) or pooled tomato diets (2.03 ± 0.45, P = 0.017) compared to controls (4.04 ± 0.65).
Carotenoid levels in plasma and skin were quantitated, with total lycopene higher in skin of tangerine fed animals despite a lower dose. Metabolomic analyses elucidated compounds derived from tomato glycoalkaloids (including tomatidine and hydroxylated-tomatidine) as significantly different metabolites in skin after tomato exposure. Here, we describe that tomato consumption can modulate risk for keratinocyte carcinomas; however, the role of the newly identified specific phytochemicals possibly responsible for this action require further investigation.
Unprotected exposure to the sun is a major risk factor in the development of skin cancer. Skin cancers, specifically keratinocyte carcinomas (KCs, often, but less accurately referred to as non melanoma skin cancers), are the most common of all cancers, with more new cases (5.4 million in 2012) each year than breast, prostate, lung and colon cancers combined. Despite a low mortality rate, KCs are costly (USD 8.1 billion/year), disfiguring, and rates are increasing, prompting the U.S. Surgeon General to release a Call to Action to prevent skin cancer. As a result, alternative methods for systemic protection, possibly via nutritional interventions to modulate risk for skin related diseases could provide significant benefit.
Human clinical data suggests that continued consumption of tomato paste can dampen UV-induced skin erythema (i.e., sunburn). It has been hypothesized that carotenoid pigments are the compounds responsible for this biological result, as one of the principal functions of carotenoids in plants is to act as photoprotectants. In plants, carotenoids help to funnel energy away from chlorophyll and the photosynthetic apparatus, and can scavenge singlet oxygen. Following consumption, carotenoids are deposited in the skin of humans where they are, in theory, present and able to protect from UV damage. Lycopene, the primary carotenoid in tomatoes, has been shown to be the most effective singlet oxygen quencher of the carotenoids. However, when comparing lycopene administered from a whole food (tomato) or a synthesized supplement, tomatoes appear more efficacious in preventing redness after UV exposure, suggesting other phytochemicals in tomatoes may additionally contribute to this effect.
The objective of this study was to determine whether dietary consumption of tomatoes (either as a tangerine or red variety), as compared to a tomato-free diet, could differentially reduce the UVB-induced tumor promotion and progression after chronic UVB exposure in male and female SKH-1 murine skin. We hypothesized that tomato consumption would decrease tumor number in animals consuming tomatoes, and that this biological effect would be the result of altered skin and plasma metabolomes.
Tumor number progression in male mice fed control diets (dotted line) vs. tangerine tomato diets (dashed line) vs. red tomato diet (solid line). Significant differences exist at end-of-study between animals on red vs. control diets, and on tomato (both diets pooled) vs. control diets.
Overall, male mice that consumed tomato-containing diets developed fewer UVB-induced skin tumors compared to male mice that did not consume tomatoes. Highly sensitive HPLC-DAD-MS/MS methods were developed to identify and quantify carotenoids in both murine plasma and skin. SKH-1 male and female mice consuming a tangerine tomato powder containing diet accumulate increased levels of lycopene in their plasma and skin despite there being about three times less lycopene in the tangerine tomato diet as compared to the red tomato diet.
This further confirms an increase in bioavailability of lycopene from tangerine tomatoes. Additionally, the concentrations of carotenoids in the skin of humans are similar to the concentrations determined in these tomato fed SKH-1 mice. Tomato alkaloids, including tomatidine, have also been documented as present in the skin of animals consuming tomato-containing diets suggesting they may be compounds responsible for the tumor number decrease noted in this study. These data suggest the need for further studies investigating the role that tomatoes and tomato phytochemicals play in the mediation of keratinocyte carcinomas.
Some complementary data