Role of Stat3 in Skin Carcinogenesis: Insights Gained from Relevant Mouse Models

Signal transducer and activator of transcription 3 (Stat3) is a cytoplasmic protein that is activated in response to cytokines and growth factors and acts as a transcription factor. Stat3 plays critical roles in various biological activities including cell proliferation, migration, and survival. Studies using keratinocyte-specific Stat3-deficient mice have revealed that Stat3 plays an important role in skin homeostasis including keratinocyte migration, wound healing, and hair follicle growth. Use of both constitutive and inducible keratinocyte-specific Stat3-deficient mouse models has demonstrated that Stat3 is required for both the initiation and promotion stages of multistage skin carcinogenesis. Further studies using a transgenic mouse model with a gain of function mutant of Stat3 (Stat3C) expressed in the basal layer of the epidermis revealed a novel role for Stat3 in skin tumor progression. Studies using similar Stat3-deficient and gain-of-function mouse models have indicated its similar roles in ultraviolet B (UVB) radiation-mediated skin carcinogenesis. This paper summarizes the use of these various mouse models for studying the role and underlying mechanisms for the function of Stat3 in skin carcinogenesis. Given its significant role throughout the skin carcinogenesis process, Stat3 is an attractive target for skin cancer prevention and treatment.

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Chemical Composition of a Novel Distillate from Fermented Mixture of Nine Anti-Inflammatory Herbs and Its UVB-Protective Efficacy in Mouse Dorsal Skin via Attenuating Collagen Disruption and Inflammation

Molecules ◽

10.3390/molecules26010124 ◽

2020 ◽

Vol 26 (1) ◽

pp. 124

Author(s):

Young Her ◽

Tae-Kyeong Lee ◽

Ji Hyeon Ahn ◽

Soon Sung Lim ◽

Beom-Goo Kang ◽

...

Keyword(s):

Topical Application ◽

Protective Efficacy ◽

Biological Activities ◽

Interleukin 1 ◽

Ultraviolet B ◽

Xanthium Strumarium ◽

Uvb Radiation ◽

Dorsal Skin ◽

Skin Damage ◽

Anti Inflammatory

Since ancient times, various herbs have been used in Asia, including Korea, China, and Japan, for wound healing and antiaging of the skin. In this study, we manufactured and chemically analyzed a novel distillate obtained from a fermented mixture of nine anti-inflammatory herbs (Angelica gigas, Lonicera japonica, Dictamnus dasycarpus Turcz., D. opposita Thunb., Ulmus davidiana var. japonica, Hordeum vulgare var. hexastichon Aschers., Xanthium strumarium L., Cnidium officinale, and Houttuynia cordata Thunb.). The fermentation of natural plants possesses beneficial effects in living systems. These activities are attributed to the chemical conversion of the parent plants to functional constituents which show more potent biological activities. In our current study, the distillate has been manufactured after fermenting the nine oriental medical plants with Lactobacillus fermentum, followed by distilling. We analyzed the chemical ingredients involved in the distillate and evaluated the effects of topical application of the distillate on ultraviolet B (UVB)-induced skin damage in Institute of Cancer Research (ICR) mice. Topical application of the distillate significantly ameliorated the macroscopic and microscopic morphology of the dorsal skin against photodamage induced by UVB radiation. Additionally, our current results showed that topical application of the distillate alleviated collagen disruption and reduced levels of proinflammatory cytokines (tumor necrosis factor alpha and interleukin 1 β expressions) in the dorsal skin against UVB radiation. Taken together, our current findings suggest that the distillate has a potential to be used as a material to develop a photoprotective adjuvant.

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Protective Effect of Spirulina-Derived C-Phycocyanin against Ultraviolet B-Induced Damage in HaCaT Cells

Medicina ◽

10.3390/medicina57030273 ◽

2021 ◽

Vol 57 (3) ◽

pp. 273

Author(s):

Young Ah Jang ◽

Bo Ae Kim

Keyword(s):

Antioxidant Defense System ◽

Skin Aging ◽

Ultraviolet B ◽

Control Group ◽

Hacat Cells ◽

Uvb Radiation ◽

Skin Damage ◽

Blue Green Algae ◽

Radiation Group ◽

Skin Wrinkles

Background and objectives: Reactive oxygen species (ROS) overwhelm the antioxidant defense system, induce oxidative stress, and increase matrix metalloproteinase (MMP) expression, resulting in skin aging. Thus, preventing ultraviolet B (UVB)-induced skin damage can attenuate skin aging. Spirulina (a biomass of cyanobacteria, also called blue-green algae) is comprised of prokaryotes, whereas microalgae are eukaryotes and are rich in phycocyanin, a powerful antioxidant. Materials and Methods: Here, we investigated the photoprotective effects of spirulina-derived C-phycocyanin (C-PC) against UVB radiation using keratinocytes (HaCaT cells). Results: UVB radiation increased MMP-1 and MMP-9 expression but decreased involucrin, filaggrin, and loricrin expression. C-PC showed no toxicity at concentrations of 5–80 μg/mL in terms of HaCaT cell viability. UVB-irradiated HaCaT cells had a 50.8% survival rate, which increased to 80.3% with C-PC treatment. MMP expression increased with UVB treatment, whereas MMP-1 and MMP-9 concentrations decreased with C-PC treatment. UVB reduced involucrin, filaggrin, and loricrin expression in HaCaT cells, but 80 μg/mL C-PC increased their expression by >25%. In the UVB radiation group, dichlorofluorescin diacetate fluorescence intensity in HaCaT cells increased by 81.6% compared with that in the control group, whereas ROS production was reduced by 51.2% and 55.1% upon treatment with 40 and 80 μg/mL C-PC, respectively. Conclusions: C-PC might reduce or prevent skin aging by reducing UVB irradiation-induced skin wrinkles and free radicals.

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Flavonoids and UV Photoprotection in Arabidopsis Mutants

Zeitschrift für Naturforschung C ◽

10.1515/znc-2001-9-1013 ◽

2001 ◽

Vol 56 (9-10) ◽

pp. 745-754 ◽

Cited By ~ 72

Author(s):

Ken G Ryan ◽

Ewald E Swinny ◽

Chris Winefield ◽

Kenneth R Markham

Keyword(s):

Crucial Role ◽

Hydroxycinnamic Acid ◽

Ultraviolet B ◽

Uvb Radiation ◽

Wild Type ◽

Hydroxycinnamic Acid Derivatives ◽

Quercetin Glycosides ◽

Kaempferol Glycosides ◽

Low Levels ◽

High Level

AbstractWild-type Arabidopsis L. leaves exposed to low ultraviolet-B (U V B ) conditions contained predominantly kaempferol glycosides, with low levels of quercetin glycosides. The flavonoid level doubled on treatment with UVB and an increase in the ratio of quercetin: kaempferol was observed. These results suggest that flavonols protect Arabidopsis plants from UVB damage, and indicate that the flavonoid 3’-hydroxylase (F3’H) enzyme, which converts dihydrokaempferol to dihydroquercetin, may play a crucial role. The tt7 mutant lacks this gene and, after treatment with sub-ambient UVB, contained kaempferol glycosides exclusively, to a level of total flavonols similar to that in wild-type Arabidopsis. Total flavonols after enhanced UVB treatment were higher in tt7 than in similarly treated wild-type plants, and only kaempferol glycosides were detected. Despite this high level, tt7 plants were less tolerant of UVB radiation than wild-type plants. These observations suggests that kaempferol is a less effective photoprotectant than quercetin. The chalcone isomerase (CHI) mutant (tt5) surprisingly did not accumulate naringenin chalcone, and this suggests that the mutation may not be restricted to the CHI gene alone. The concentration of hydroxycinnamic acid derivatives did not change with UVB treatment in most varieties indicating that their role in UV photoprotection may be subordinate to that of the flavonoids.

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UV radiation effects on the embryos of anchoveta (Engraulis ringens) and common sardine (Strangomera bentincki) off central Chile

Marine and Freshwater Research ◽

10.1071/mf14038 ◽

2016 ◽

Vol 67 (2) ◽

pp. 195 ◽

Cited By ~ 4

Author(s):

P. Vásquez ◽

A. Llanos-Rivera ◽

L. R. Castro ◽

C. Fernandez

Keyword(s):

Vertical Distribution ◽

Water Column ◽

Radiation Effects ◽

Hatching Success ◽

Sublethal Effects ◽

Ultraviolet B ◽

Uvb Radiation ◽

Central Chile ◽

Fish Embryos ◽

Engraulis Ringens

It has been proposed that current levels of ultraviolet B (UVB) radiation could cause lethal or sublethal effects on fish embryos located in the upper layers of the water column. Observed levels of UVB off central Chile (36°S, 73°W) indicate that planktonic fish embryos could be exposed to harmful UVB radiation. From July 2011 to January 2012 embryos from anchoveta (Engraulis ringens) and common sardine (Strangomera bentincki) were used to test experimentally whether the UVB levels in central Chile produce lethal or sublethal effects in epipelagic fish embryos. Simultaneously, whether the embryos might be exposed to harmful UVB levels in the field was investigated. Our experimental results show that UVB may cause a decrease in hatching success, changes in buoyancy and embryonic malformations. These results, along with the observed vertical distribution of embryos and UVB radiation levels in the field during late spring suggest that lethal and sublethal effects may be occurring in the embryos of both species.

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Long-term UVB exposure promotes predator-inspection behaviour in a fish

Biology Letters ◽

10.1098/rsbl.2017.0497 ◽

2017 ◽

Vol 13 (12) ◽

pp. 20170497 ◽

Cited By ~ 2

Author(s):

Simon Vitt ◽

Janina E. Zierul ◽

Theo C. M. Bakker ◽

Ingolf P. Rick

Keyword(s):

Gasterosteus Aculeatus ◽

Stratospheric Ozone ◽

Ultraviolet B ◽

Antipredator Behaviour ◽

Uvb Radiation ◽

Ecological Processes ◽

Predator Prey ◽

Natural Sunlight ◽

Predator Inspection

Ultraviolet-B radiation (UVB) reaching the earth's surface has increased due to human-caused stratospheric ozone depletion. Whereas the harmful effects of UVB on aquatic organisms are well studied at the molecular and cellular level, recent studies have also begun to address behavioural changes caused by sublethal amounts of UVB. However, the behavioural consequences of long-term exposure to ecologically relevant UVB levels over several life stages are virtually unknown, particularly with regard to predator–prey behaviour. We found increased predator-inspection behaviour together with a smaller body length in three-spined sticklebacks ( Gasterosteus aculeatus ) after fish were exposed for about seven months to natural sunlight conditions with enhanced UVB, compared with full siblings exposed to natural sunlight only. The observed change in antipredator behaviour may reflect a direct behavioural response mediated through UVB-induced oxidative stress during development. Alternatively, the smaller body size in UVB-exposed fish may result in an increased inspection effort allowing them to spend more time foraging. Our findings suggest that, within the scope of environmental change, UVB radiation constitutes an important stress factor by eliciting behavioural responses that influence crucial ecological processes, such as predator–prey interactions.

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Pterostilbene Supplementation Inhibits Early Inflammatory Response and Oxidative Stress in UVB-Induced BALB/C Mice

Sains Malaysiana ◽

10.17576/jsm-2021-5005-19 ◽

2021 ◽

Vol 50 (5) ◽

pp. 1407-1414

Author(s):

Tava Shelan Nagapan ◽

Wenna Nallance Lim ◽

Ahmad Rohi Ghazali ◽

Dayang Fredalina Basri

Keyword(s):

Biological Activities ◽

Skinfold Thickness ◽

Treated Group ◽

Ultraviolet B ◽

Epidermal Hyperplasia ◽

Sod Activity ◽

Uvb Irradiation ◽

Early Inflammatory Response ◽

Antioxidant Agent ◽

And Oxidative Stress

Extended dermal exposure of ultraviolet B (UVB) can induce erythema, hyperpigmentation, epidermal hyperplasia and cancer. Natural active compound such as pterostilbene (PS) is a potential UV-protecting agent as it has broad biological activities. This study aimed to evaluate the photoprotective effect of pterostilbene on ultraviolet-B-induced BALB/c mice. Twenty-four female mice were randomised into four groups (n=6/group): vehicle control (VC); UVB irradiated only (UVB only); UVB irradiation treated with pterostilbene 10 mg/kg (PS10+UVB); (iv) UVB irradiation treated with pterostilbene 20 mg/kg (PS20+UVB). The PS treatments were given for 14 days, and UVB was given at dose 250 mJ/cm2 on days 9, 11, and 13 of the treatment periods. The results showed that PS lessened redness and scaling on the skin of UVB-irradiated mice. The skinfold thickness and epidermal thickness in the PS-treated group were significantly reduced (p<0.05) in comparison with those in the UVB only group. The PS10 and PS20 groups (5.927 ± 0.354 and 5.660 ± 0.765 nmol/g, respectively) demonstrated significantly decreased MDA levels (P<0.05) relative to the UVB only group (13.343 ± 1.350 nmol/g). The GSH level in both PS10 (0.555 ± 0.020 µmol/mg) and PS20 (0.568 ± 0.055 µmol/mg) groups increased significantly (p<0.05) compared with that in the UVB only group (0.376 ± 0.025 µmol/mg). SOD activity in the PS20 group (1.388 ± 0.172 U/min/mg) increased significantly (p<0.05) compared with that in the UVB only group (0.561 ± 0.034 U/min/mg). Histological observation showed that PS reduced leukocyte infiltration and epidermal hyperplasia. Hence, oral PS may exert a photoprotective effect by acting as an anti-inflammatory and antioxidant agent on UVB-irradiated mice skin.

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hSSB2 (NABP1) is required for the recruitment of RPA during the cellular response to DNA UV damage

Scientific Reports ◽

10.1038/s41598-021-99355-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Didier Boucher ◽

Ruvini Kariawasam ◽

Joshua Burgess ◽

Adrian Gimenez ◽

Tristan E. Ocampo ◽

...

Keyword(s):

Dna Damage ◽

Cellular Response ◽

Excision Repair ◽

Protein A ◽

Ultraviolet B ◽

Repair System ◽

Uvb Radiation ◽

Exogenous Dna

AbstractMaintenance of genomic stability is critical to prevent diseases such as cancer. As such, eukaryotic cells have multiple pathways to efficiently detect, signal and repair DNA damage. One common form of exogenous DNA damage comes from ultraviolet B (UVB) radiation. UVB generates cyclobutane pyrimidine dimers (CPD) that must be rapidly detected and repaired to maintain the genetic code. The nucleotide excision repair (NER) pathway is the main repair system for this type of DNA damage. Here, we determined the role of the human Single-Stranded DNA Binding protein 2, hSSB2, in the response to UVB exposure. We demonstrate that hSSB2 levels increase in vitro and in vivo after UVB irradiation and that hSSB2 rapidly binds to chromatin. Depletion of hSSB2 results in significantly decreased Replication Protein A (RPA32) phosphorylation and impaired RPA32 localisation to the site of UV-induced DNA damage. Delayed recruitment of NER protein Xeroderma Pigmentosum group C (XPC) was also observed, leading to increased cellular sensitivity to UVB. Finally, hSSB2 was shown to have affinity for single-strand DNA containing a single CPD and for duplex DNA with a two-base mismatch mimicking a CPD moiety. Altogether our data demonstrate that hSSB2 is involved in the cellular response to UV exposure.

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