astaxanthine and Skin-Neoplasms

Every day, we come into contact with ultraviolet radiation (UVR). If under medical supervision, small amounts of UVR could be beneficial, the detrimental and hazardous effects of UVR exposure dictate an unbalance towards the risks on the risk-benefit ratio. Acute and chronic effects of ultraviolet-A and ultraviolet-B involve mainly the skin, the immune system, and the eyes. Photodamage is an umbrella term that includes general phototoxicity, photoaging, and cancer caused by UVR. All these phenomena are mediated by direct or indirect oxidative stress and inflammation and are strictly connected one to the other. Astaxanthin (ASX) and fucoxanthin (FX) are peculiar marine carotenoids characterized by outstanding antioxidant properties. In particular, ASX showed exceptional efficacy in counteracting all categories of photodamages, in vitro and in vivo, thanks to both antioxidant potential and activation of alternative pathways. Less evidence has been produced about FX, but it still represents an interesting promise to prevent the detrimental effect of UVR. Altogether, these results highlight the importance of digging into the marine ecosystem to look for new compounds that could be beneficial for human health and confirm that the marine environment is as much as full of active compounds as the terrestrial one, it just needs to be more explored.

Topics: Animals; Anti-Inflammatory Agents; Anticarcinogenic Agents; Antioxidants; Humans; Inflammation Mediators; Neoplasms, Radiation-Induced; Oxidative Stress; Skin; Skin Aging; Skin Neoplasms; Sunburn; Sunscreening Agents; Xanthophylls

The present study investigated effects of low-level laser therapy with cellulose nanocrystals/cellulose nanofibrils loaded in nanoemulsion (NE) against skin cancer cells on apoptosis. The nanoemulsion was fabricated and characterized by the standard methods. The toxicity level by cytotoxicity assays, generation of reactive singlet oxygen (ROS) and antioxidant potential, cell proliferation and migration were confirmed by using standard assays. The cellular uptake efficacy was evaluated by differential staining. The protein levels of EGFR, PI3K, AKT, ERK, GAPDH, and β-actin were detected by western blot. The samples showed a spherical shaped structure with the average size confirmed strong and stable hydrogen bonding forces with high degradation temperature and endothermic transition peaks. The fabricated samples showed no toxicity and high cell proliferation by generating more singlet oxygen levels and antioxidants. The intracellular signaling pathways was regulated with high protein expression levels, which was stimulated by specific molecules for cell proliferation, migration, and differentiation in cancer cells. The results proved that combined treatment regulated the intracellular signaling pathways in cancer cells. The current study showed a novel strategy for improving therapeutic efficacy of nanoemulsion by using low-level laser therapy. Further, the current favorable outcomes will be evaluated in in vivo animal models.

Topics: Animals; Apoptosis; Cellulose; Emulsions; Mice; Mitochondria; Nanoparticles; NIH 3T3 Cells; Reactive Oxygen Species; Skin Neoplasms; Xanthophylls

Nuclear factor erythroid-2-related factor-2 (Nrf2 or NFE2L2) is a master regulator of the anti-oxidative stress response, which is involved in the defense against many oxidative stress/inflammation-mediated diseases, including anticancer effects elicited by an increasing number of natural products. Our previous studies showed that the epigenetic modification of the Nrf2 gene plays a key role in restoring the expression of Nrf2. In this study, we aimed to investigate the epigenetic regulation of Nrf2 by astaxanthin (AST) and fucoxanthin (FX), carotenoids which are abundant in microalgae and seaweeds, in mouse skin epidermal JB6 P+ cells. FX induced the anti-oxidant response element (ARE)-luciferase and upregulated the mRNA and protein levels of Nrf2 and Nrf2 downstream genes in HepG2-C8 cells overexpressing the ARE-luciferase reporter. Both FX and AST decreased colony formation in 12-Otetradecanoylphorbol-13-acetate (TPA)-induced transformation of JB6 P+ cells. FX decreased the methylation of the Nrf2 promoter region in the JB6 P+ cells by the bisulfite conversion and pyrosequencing. Both FX and AST significantly reduced DNA methyltransferase (DNMT) activity but did not affect histone deacetylase (HDAC) activity in JB6 P+ cells. In summary, our results show that FX activates the Nrf2 signaling pathway, induces the epigenetic demethylation of CpG sites in Nrf2 and blocks the TPA-induced transformation of JB6 P+ cells, indicating the potential health-promoting effects of FX in skin cancer prevention.

Topics: Animals; Antioxidant Response Elements; Cell Transformation, Neoplastic; CpG Islands; DNA Demethylation; Epidermal Cells; Epigenesis, Genetic; Gene Knockdown Techniques; Hep G2 Cells; Humans; Mice; NF-E2-Related Factor 2; RNA, Small Interfering; Signal Transduction; Skin Neoplasms; Tetradecanoylphorbol Acetate; Xanthophylls

Astaxanthin mono- (AXME) and diesters (AXDE) were characterized and examined for anticancer potency with total carotenoids (TC) and astaxanthin (AX) against UV-7,12-dimethylbenz(a)anthracene (DMBA)-induced skin cancer model in rat. At 200 μg/kg bw, AXDE and AXME reduced UV-DMBA-induced tumor incidences up to 96 and 88%, respectively, when compared to AX (66%) and TC (85%). UV-DMBA has been known to generate high levels of free radicals and tyrosinase enzyme, leading to characteristic symptoms of skin pigmentation and tumor initiation. Intriguingly, ~7-fold increase in tyrosinase and 10-fold decrease in antioxidant levels were normalized by AXDE and AXME as opposed to only ~1.4-2.2-fold by AX and TC, respectively. This result together with the appearance of 72 and 58 ng/mL of retinol in the serum of respective AXE-treated (AXDE + AXME) and AX-treated animals suggested that better anticancer potency of AXEs could be due to increased bioavailability.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Antioxidants; Biological Availability; Carcinogens; Chlorophyta; Esters; Monophenol Monooxygenase; Rats; Rats, Wistar; Skin Neoplasms; Vitamin A; Xanthophylls

Astaxanthin captured peroxynitrite to form nitroastaxanthins. 15-Nitroastaxanthin was a major reaction product of astaxanthin with peroxynitrite. Here, the anti-oxidative, anti-tumor-promoting, and anti-carcinogensis activities of 15-nitroastaxanthin were investigated. In addition to astaxanthin, 15-nitroastaxanthin showed excellent singlet oxygen quenching activity. Furthermore, 15-nitroastaxanthin showed inhibitory effects of in vitro Epstein-Barr virus early antigen activation and two-stage carcinogensis on mouse skin papillomas. These activities were slightly higher than those of astaxanthin. Similar results were obtained for the 15-nitrolutein, a major reaction product of lutein with peroxynitrite.

Topics: Animals; Anticarcinogenic Agents; Antigens, Viral; Antineoplastic Agents; Antioxidants; Cell Transformation, Neoplastic; Female; Lutein; Mice; Mice, Inbred ICR; Papilloma; Peroxynitrous Acid; Skin Neoplasms; Tyrosine; Xanthophylls

Studies employing time-resolved techniques have shown that beta-carotene, astaxanthin, and lycopene behave quite distinctly with respect to radical quenching and stability, lycopene being the least stable. These results are compatible with the relative effects of the various carotenoids on ultraviolet (UV)-mediated carcinogenesis in mice in which a statistically significant exacerbation by beta-carotene and astaxanthin, but not by lycopene, was observed. Interactions between these carotenoids and vitamin C and E radicals not only provide a chemical basis to explain the failure of beta-carotene to provide benefit in recent clinical trials but suggest that future carotenoid supplementation studies should proceed with caution until carotenoid interactions and radical repair mechanism(s) are elucidated.

Topics: Animals; Anticarcinogenic Agents; beta Carotene; Carcinogenicity Tests; Carotenoids; Dietary Supplements; Female; Free Radicals; Lycopene; Mice; Mice, Hairless; Neoplasms, Radiation-Induced; Random Allocation; Skin Neoplasms; Ultraviolet Rays; Xanthophylls

Solar radiations (UV A and B) can cause epidermis photoaging and skin cancers. These frequently irreversible effects result from the in situ generation of free radicals. However, it has been noted that nutritional factors can modulate photochemical damage, in particular the common carotenoids present in food, which can be considered as potential prophylactic agents against carcinogenesis. We investigated the effect of UV A and B radiations on the skin of the SKH1 hairless mouse fed a diet either lacking in vitamin A or supplemented with retinol, beta-carotene or astaxanthin. The latter is an oxygenated carotenoid (like canthaxanthin) without provitamin A activity and with strong singlet oxygen quenching ability. After analysing of vitamin status of each group (plasma retinol concentrations and hepatic reserves), we searched for UV-induced modifications of polyamine metabolism by measuring epidermal ornithine decarboxylase (ODC) activity and free polyamines concentration (putrescine, spermidine and spermine). In the basal state without irradiation, differences in ODC activity between groups were nonsignificant; but after UV stimulation, ODC increased markedly in the skin of vitamin A-deficient animals, much more than in other groups. Curiously, the addition of astaxanthin or beta-carotene to the regimen containing retinol reduced the protective effect of retinol alone. Regarding polyamines after irradiation, putrescine was significantly increased in the skin of deficient animals, in parallel with ODC activity. However, astaxanthin had a stronger inhibitory effect on putrescine accumulation than retinol, and decreased spermidine and spermine concentrations: this suggests a specific action on transglutaminases.

Topics: Animals; beta Carotene; Carotenoids; Epidermis; Female; Food, Fortified; Liver; Mice; Mice, Hairless; Neoplasms, Radiation-Induced; Nutritional Status; Ornithine Decarboxylase; Polyamines; Putrescine; Random Allocation; Skin; Skin Neoplasms; Spermidine; Spermine; Ultraviolet Rays; Vitamin A; Vitamin A Deficiency; Xanthophylls