Dietary Lycopene Protects SKH-1 Mice Against Ultraviolet B-Induced Photocarcinogenesis

Lycopene, an acyclic hydrocarbon, non-provitamin A carotenoid, is a potent antioxidant with well-documented anticancer properties. In this study, we investigated the effects of dietary lycopene on sub-acute and chronic ultraviolet B (UVB)-induced skin carcinogenesis in SKH-1 mice. Groups of three mice were fed with a nonsupplemented or 1% lycopene diet for two weeks before and throughout two weeks of UVB irradiation (30 mJ/cm2 UVB, thrice weekly). The lycopene diet significantly reduced the formation of pyrimidine dimers (PDs) and the expression of proliferative cellular nuclear antigen (PCNA) in UVB-irradiated skin. Then groups of eighteen mice were each fed with control diet or with a 0.25% or 1% (w/w) lycopene-supplemented diet for 40 weeks, beginning one week before UVB irradiation (30 mJ/cm2 UVB, thrice weekly for 23 weeks) and continuing after termination of UVB. Lycopene significantly inhibited the onset and decreased the incidence, multiplicity, and tumor weights of UVB-induced skin tumors. UVB-induced epidermal hyperplasia and PCNA expression were still remarkably inhibited by dietary lycopene, even up to 40 weeks. No significant difference in protection was detected between the low and high concentrations of lycopene. These results demonstrate that dietary lycopene does protect against UVB-induced epidermal hyperplasia and carcinogenesis. J Drugs Dermatol. 2019;18(12):1244-1254.

Protection From Environmental Skin Damage With Topical Antioxidants.

Skin is an efficient protective barrier armed with an intricate network of antioxidants. External environmental stress diminishes and sometimes overwhelms these innate protective mechanisms; aging slows their efficacy. Topical antioxidants enhance natural endogenous defenses to create an indwelling reservoir for sustained protection with far higher concentrations than possible with oral intake. The challenge is creating formulations of these labile molecules that are stable, active, and can be effectively absorbed transdermally to deliver high concentrations.

Mechanisms of aging and development-A new understanding of environmental damage to the skin and prevention with topical antioxidants.

Recent research has given us new insights into the molecular biology of extrinsic aging of the skin. Not only does UV irradiation directly cause photoaging of the skin, but also environmental pollutants significantly damage exposed skin by several mechanisms. Exposure to the noxious gases of air pollution with simultaneous exposure to UVA can act synergistically to initiate skin cancer. Also ozone generated from pollutants reacting with UV induces oxidative stress of the skin's surface via formation of lipid peroxidation products, with cascading consequences to deeper layers. Furthermore, new studies have demonstrated that particulate matter (PM) pollutants can penetrate the skin transepidermally and through hair follicles to induce skin aging via the aryl hydrocarbon receptor (AHR), a recently discovered ligand-activated transcription factor that regulates and protects keratinocytes, melanocytes, and fibroblasts. With this understanding that extrinsic aging of the skin is not only due to photoaging, we realize the necessity of protection beyond sunscreen. Fortunately, correctly formulated topical antioxidants can prevent damage inflicted by both UV and environmental pollution.

The effects of topical L-selenomethionine on protection against UVB-induced skin cancer when given before, during, and after UVB exposure.

Previous studies in mice have shown that topical L-selenomethionine (SeMet) can prevent UVB-induced skin cancer when applied continuously before, during, and after the radiation exposure. With topical application of SeMet, selenium levels were shown to increase in the skin and liver, as well as in tumor tissue. Thus, possibly, the timing of SeMet application could affect the degree of inhibition of UVB-tumorigenesis (or maybe even enhance tumorigenesis at some stage). The goal of this research was to determine whether topical SeMet best inhibits UV-induced skin cancer if (a) begun before and continued during and after UVB exposure, (b) if begun before UVB-exposure and discontinued when tumors are first clinically detected, or (c) if begun only after tumors are first detected and continued thereafter. Groups of ten Skh: 1 hairless, non-pigmented mice were treated topically with vehicle lotion, or with SeMet (0.05%) in that vehicle lotion applied either (a) before, during, and after UV exposure, (b) before UV radiation and continued only until the first tumor was detected, or (c) only after the first tumor was detected. In all cases, UV irradiation was discontinued at the time of detection of the first tumor. Optimal inhibition of skin cancer was achieved by application of topical SeMet before, during, and after exposure; significant protection was also attained with application only after the onset of tumors. Notably, statistically significant protection was not seen with SeMet application only prior to tumor detection. These results suggest that even beginning SeMet supplementation late in the process of tumorigenesis can help protect from UV-induced photodamage and skin cancer.

Interaction of vitamins C and E as better cosmeceuticals.

Although many cosmeceutical formulations contain vitamin C and/or vitamin E, very few are actually effective in topical application. First because there is only a low concentration, second because the stability is compromised as soon as the product is opened and exposed to air and light, and third because the form of the molecule (an ester or a mixture of isomers) is not absorbed or metabolized effectively by the skin. However, when a stable formulation delivers a high concentration of the nonesterified, optimal isomer of the antioxidant, vitamins C and E do indeed inhibit the acute ultraviolet (UV) damage of erythema, sunburn, and tanning as well as chronic UV photoaging and skin cancer. Both are highly effective depigmenting agents. Topical vitamin C also increases collagen synthesis in both young and old fibroblasts. Because vitamin C regenerates oxidized vitamin E, the combination in a cosmeceutical formulation is synergistic - particularly in UV protection.

Effects of topical L-selenomethionine with topical and oral vitamin E on pigmentation and skin cancer induced by ultraviolet irradiation in Skh:2 hairless mice.

BACKGROUND: The antioxidants selenium and vitamin E can be effective in reducing acute and chronic ultraviolet (UV)-induced skin damage. OBJECTIVE: This study investigated whether topical L-selenomethionine with topical RRR-alpha-tocopherol (Eol) or oral RRR-alpha-tocopheryl acetate (Eac) can reduce the incidence of UV-induced skin damage more than treatment with each alone. METHODS: Skh:2 hairless pigmented mice were treated with lotion vehicle, L-selenomethionine lotion, Eol lotion, oral Eac, L-selenomethionine plus Eol lotion, or L-selenomethionine lotion plus oral Eac and exposed to UVB. Skin pigmentation was scored, and the number of skin tumors per animal was counted weekly. RESULTS: Mice treated with selenium and vitamin E had significantly less acute and chronic UV-induced skin damage. CONCLUSION: Topical L-selenomethionine alone and combined with vitamin E gave the best protection against UV-induced blistering and pigmentation. In protecting against skin cancer, topical Eol and topical L-selenomethionine plus oral Eac were best. Significant synergy of L-selenomethionine with vitamin E was not observed.