Nabumetone induced photogenotoxicity mechanism mediated by ROS generation under environmental UV radiation in human keratinocytes (HaCaT) cell line.

Nabumetone (NB) is a non-steroidal anti-inflammatory drug (NSAID), prescribed for managing pain associated with acute/chronic rheumatoid arthritis, osteoarthritis and other musculoskeletal disorders. Though some incidences of photosensitivity have been reported, there is limited information available on its phototoxicity potential. In this study, NB photodegraded in a time-dependant manner (0-4 h) under UVA (1.5 mW/cm2), UVB (0.6 mW/cm2) and natural sunlight as observed through UV-vis spectrophotometer and the results were further confirmed with Ultra High-Performance Liquid Chromatography (UHPLC). Photosensitized NB generated reactive oxygen species (ROS) as observed by lipid peroxidation, suggesting oxidative degradation of lipids in cell membrane, thereby resulting in cell damage. MTT and NRU (neutral red uptake) assays revealed that NB induced phototoxicity in concentration-dependent manner (0.5, 1, 5, 10 µg/ml) under UVA, UVB and sunlight exposure (30 min) in human keratinocytes cell line (HaCaT), with significant phototoxicity at the concentration of 5 µg/ml. Photosensitized NB generated intracellular ROS, disrupted mitochondrial and lysosomal membrane integrity, resulting in cell death. UV-induced genotoxicity by NB was confirmed through micronuclei generation, γ-H2AX induction and cyclobutane pyrimidine dimer formation. This is the first study which showed the phototoxicity and photogenotoxicity potential of NB in HaCaT cell line. We also observed that photosensitized NB upregulated inflammatory markers, such as COX-2 and TNFα. This study proposes that sunlight exposure should be avoided by patients using nabumetone and proper guidance should be provided by clinicians regarding photosensitivity of drugs for better safety and efficacy.

Oxidative stress-mediated photoactivation of carbazole inhibits human skin cell physiology.

Prolonged exposure of the earth's surface to the sun's ultraviolet radiation may result in various skin diseases and cataract. Carbazole (CBZ), as a polycyclic-aromatic hydrocarbon (PAH), is blended with a five-member nitrogen-containing ring. It is found in cigarette smoke, coal, eye kohl, tattoo ink, and wood combustion and affects various types of flora and fauna. Our findings suggest that CBZ generates reactive oxygen species (ROS) like O2•- through type-I photodynamic reaction and causes phototoxicity in the human keratinocyte cell line (HaCaT), which has been proved by mitochondrial dehydrogenase and neutral red uptake assays. CBZ induces single strand DNA damage. We have investigated the involvement of the apoptotic pattern of cell death and confirmed it by cytochrome C release from mitochondria and caspase-9 activation. Similarly, photo-micronuclei formation was associated to CBZ-induced phototoxicity. The results of this study strongly support that the upregulation of bax, cyto-C, apaf-1, casp-9 and down regulation of bcl2, keap-1, nrf-2, and hmox-1 genes cause apoptopic cell death. Downregulation of antioxidant genes showed a significant amount of ROS generation by photosensitized CBZ. Therefore, the current study will be a step forward to safeguard human beings from sunlight-induced photosensitive CBZ prolonged exposure.

Photoexcited triclosan induced DNA damage and oxidative stress via p38 MAP kinase signaling involving type I radicals under sunlight/UVB exposure.

Triclosan (TCS) is an antimicrobial preservative used in personal care products. Here, we have studied the phototoxicity, photogenotoxicity of TCS and its molecular mechanism involving p38 mitogen activated protein kinase (MAPK) pathway under UVB/sunlight exposure. We found that TCS showed photodegradation and photoproducts formation under UVB/sunlight. In silico study suggests that photosensitized TCS loses its preservative property due to the formation of its photoproducts. Photosensitized TCS induces significant O2•-, •OH generation and lipid peroxidation via type-I photochemical reaction mechanism under UVB/sunlight exposure. We performed intracellular study of TCS on human skin keratinocytes (HaCaT cell-line) under the ambient intensity of UVB (0.6 mW/cm2) and sunlight exposure. Significant intracellular ROS generation was observed through DCFH2-DA/DHE assays along with a significant reduction in cell viability through MTT and NRU assays in photosensitized TCS. Photosensitized TCS also induces endoplasmic reticulum (ER) stress as shown through ER-tracker/DAPI staining and Ca2+ release. It further induced cell cycle arrest through the sub-G1 phase augmentation and caused lysosomal/mitochondrial destabilization. Photogenotoxicity was shown through significant tail DNA, micronuclei and cyclobutane pyrimidine dimers (CPDs) formations. Cell signaling mechanism implicated upregulated expression of cleaved Caspase-3, Bax, phospho-p38, phospho-JNK and cytochrome C, thereby downregulated Bcl-2 expressions. Results advocate that TCS induces phototoxic effects via type I mediated photodynamic mechanism and activation of MAPK pathway. We conclude that photoexcited TCS may be deleterious to human health at the ambient environmental intensities of sunlight reaching at the earth's surface. Therefore, it may be replaced by alternative safe preservative.

Combined effect of Benzophenone-2 and ultraviolet radiation promote photogenotoxicity and photocytotoxicity in human keratinocytes.

Benzophenone-2 (BP2), a common ingredient of sunscreens formulation is widely used as UV filter. We have assessed the photogenotoxic and photocytotoxic potential of BP2. Photostability test showed that BP2 is unstable under UV exposure. Cell proliferation assay revealed that viability of HaCaT cells significantly reduced under UVA, UVB and sunlight exposure. DCF fluorescence intensity proved intracellular ROS generation capacity of BP2 under sunlight, UVA and UVB irradiation. Photodynamic degradation of guanine base of DNA is promoted by BP2 under UV treatment. Genotoxicity assessed by comet assay, showed that photosensitized BP2 enhanced DNA damage, which is measured in term of % tail DNA and olive tail moment. Genotoxic potential of BP2 was further validated with photomicronuclei assay. Photogenotoxicity of BP2 was lastly confirmed by formation of CPDs (Cyclo butane pyrimidine dimmers). DNA damage induced by BP2 was irreversible and extended incubation periods (6-12 h) not favored the recovery from damaged DNA. JC 1 staining showed significant reduction in mitochondrial membrane potential. Membrane integrity compromisation of HaCaT cells was established by AO (Acridine orange), EtBr (Ethidium bromide) staining and confirmed with sub G1 population of cell cycle. Thus, results suggest that BP2 should be avoided in topical application for safe sunscreen practices.

Dynamin-related Protein 1 Inhibition Mitigates Bisphenol A-mediated Alterations in Mitochondrial Dynamics and Neural Stem Cell Proliferation and Differentiation.

The regulatory dynamics of mitochondria comprises well orchestrated distribution and mitochondrial turnover to maintain the mitochondrial circuitry and homeostasis inside the cells. Several pieces of evidence suggested impaired mitochondrial dynamics and its association with the pathogenesis of neurodegenerative disorders. We found that chronic exposure of synthetic xenoestrogen bisphenol A (BPA), a component of consumer plastic products, impaired autophagy-mediated mitochondrial turnover, leading to increased oxidative stress, mitochondrial fragmentation, and apoptosis in hippocampal neural stem cells (NSCs). It also inhibited hippocampal derived NSC proliferation and differentiation, as evident by the decreased number of BrdU- and ß-III tubulin-positive cells. All these effects were reversed by the inhibition of oxidative stress using N-acetyl cysteine. BPA up-regulated the levels of Drp-1 (dynamin-related protein 1) and enhanced its mitochondrial translocation, with no effect on Fis-1, Mfn-1, Mfn-2, and Opa-1 in vitro and in the hippocampus. Moreover, transmission electron microscopy studies suggested increased mitochondrial fission and accumulation of fragmented mitochondria and decreased elongated mitochondria in the hippocampus of the rat brain. Impaired mitochondrial dynamics by BPA resulted in increased reactive oxygen species and malondialdehyde levels, disruption of mitochondrial membrane potential, and ATP decline. Pharmacological (Mdivi-1) and genetic (Drp-1siRNA) inhibition of Drp-1 reversed BPA-induced mitochondrial dysfunctions, fragmentation, and apoptosis. Interestingly, BPA-mediated inhibitory effects on NSC proliferation and neuronal differentiations were also mitigated by Drp-1 inhibition. On the other hand, Drp-1 inhibition blocked BPA-mediated Drp-1 translocation, leading to decreased apoptosis of NSC. Overall, our studies implicate Drp-1 as a potential therapeutic target against BPA-mediated impaired mitochondrial dynamics and neurodegeneration in the hippocampus.

Activation of Autophagic Flux against Xenoestrogen Bisphenol-A-induced Hippocampal Neurodegeneration via AMP kinase (AMPK)/Mammalian Target of Rapamycin (mTOR) Pathways.

The human health hazards related to persisting use of bisphenol-A (BPA) are well documented. BPA-induced neurotoxicity occurs with the generation of oxidative stress, neurodegeneration, and cognitive dysfunctions. However, the cellular and molecular mechanism(s) of the effects of BPA on autophagy and association with oxidative stress and apoptosis are still elusive. We observed that BPA exposure during the early postnatal period enhanced the expression and the levels of autophagy genes/proteins. BPA treatment in the presence of bafilomycin A1 increased the levels of LC3-II and SQSTM1 and also potentiated GFP-LC3 puncta index in GFP-LC3-transfected hippocampal neural stem cell-derived neurons. BPA-induced generation of reactive oxygen species and apoptosis were mitigated by a pharmacological activator of autophagy (rapamycin). Pharmacological (wortmannin and bafilomycin A1) and genetic (beclin siRNA) inhibition of autophagy aggravated BPA neurotoxicity. Activation of autophagy against BPA resulted in intracellular energy sensor AMP kinase (AMPK) activation, increased phosphorylation of raptor and acetyl-CoA carboxylase, and decreased phosphorylation of ULK1 (Ser-757), and silencing of AMPK exacerbated BPA neurotoxicity. Conversely, BPA exposure down-regulated the mammalian target of rapamycin (mTOR) pathway by phosphorylation of raptor as a transient cell's compensatory mechanism to preserve cellular energy pool. Moreover, silencing of mTOR enhanced autophagy, which further alleviated BPA-induced reactive oxygen species generation and apoptosis. BPA-mediated neurotoxicity also resulted in mitochondrial loss, bioenergetic deficits, and increased PARKIN mitochondrial translocation, suggesting enhanced mitophagy. These results suggest implication of autophagy against BPA-mediated neurodegeneration through involvement of AMPK and mTOR pathways. Hence, autophagy, which arbitrates cell survival and demise during stress conditions, requires further assessment to be established as a biomarker of xenoestrogen exposure.

Photosensitized 2-amino-3-hydroxypyridine-induced mitochondrial apoptosis via Smac/DIABLO in human skin cells.

The popularity of hair dyes use has been increasing regularly throughout the world as per the demand of hair coloring fashion trends and other cosmetic products. 2-Amino-3-hydroxypyridine (A132) is widely used as a hair dye ingredient around the world. We are reporting first time the phototoxicity mechanism of A132 under ambient environmental UV-B radiation. It showed maximum absorption in UV-B region (317 nm) and forms a photoproduct within an hour exposure of UV-B irradiation. Photocytotoxicity of A132 in human keratinocytes (HaCaT) was measured by mitochondrial (MTT), lysosomal (NRU) and LDH assays which illustrated the significant reduction in cell viability. The role of reactive oxygen species (ROS) generation for A132 phototoxicity was established photo- chemically as well as intracellularly. Noteworthy, formation of tail DNA (comet assay), micronuclei and cyclobutane pyrimidine dimers (CPDs) (immunocytochemistry) formation confirmed the photogenotoxic potential of dye. Cell cycle study (sub-G1peak) and staining with EB/AO revealed the cell cycle arrest and apoptosis. Further, mitochondrial mediated apoptosis was corroborated by reduced MMP, release of cytochrome c and upregulation of caspase-3. Release of mitochondrial Smac/DIABLO in cytoplasm demonstrated the caspase dependent apoptotic cell death by photolabile A132 dye. In-addition increased Bax/Bcl2 ratio again proved the apoptosis. Thus, study suggests that A132 induces photogenotoxicity, phototoxicity and apoptotic cell death through the involvement of Smac/DIABLO in mitochondrial apoptosis via caspase dependent manner. Therefore, the long term use of A132 dye and sunlight exposure jointly increased the oxidative stress in skin which causes premature hair loss, damage to progenitor cells of hair follicles.

Attenuated neuroprotective effect of riboflavin under UV-B irradiation via miR-203/c-Jun signaling pathway in vivo and in vitro.

BACKGROUND: Riboflavin (RF) or vitamin B2 is known to have neuroprotective effects. In the present study, we report the attenuation of the neuroprotective effects of RF under UV-B irradiation. Preconditioning of UV-B irradiated riboflavin (UV-B-RF) showed attenuated neuroprotective effects compared to that of RF in SH-SY5Y neuroblostoma cell line and primary cortical neurons in vitro and a rat model of cerebral ischemia in vivo. RESULTS: Results indicated that RF pretreatment significantly inhibited cell death and reduced LDH secretion compared to that of the UV-B-RF pretreatment in primary cortical neuron cultures subjected to oxygen glucose deprivation in vitro and cortical brain tissue subjected to ischemic injury in vivo. Further mechanistic studies using cortical neuron cultures revealed that RF treatment induced increased miR-203 expression which in turn inhibited c-Jun expression and increased neuronal cell survival. Functional assays clearly demonstrated that the UV-B-RF preconditioning failed to sustain the increased expression of miR-203 and the decreased levels of c-Jun, mediating the neuroprotective effects of RF. UV-B irradiation attenuated the neuroprotective effects of RF through modulation of the miR-203/c-Jun signaling pathway. CONCLUSION: Thus, the ability of UV-B to serve as a modulator of this neuroprotective signaling pathway warrants further studies into its role as a regulator of other cytoprotective/neuroprotective signaling pathways.

Photosensitized mefloquine induces ROS-mediated DNA damage and apoptosis in keratinocytes under ambient UVB and sunlight exposure.

The present study illustrates the photosensitizing behavior of mefloquine (MQ) in human skin keratinocytes under ambient doses of UVB and sunlight exposure. Photochemically, MQ generated reactive oxygen species superoxide radical, hydroxyl radical, and singlet oxygen through type I and type II photodynamic reactions, respectively, which caused photooxidative damage to DNA and formed localized DNA lesions cyclobutane pyrimidine dimers. Photosensitized MQ reduced the viability of keratinocytes to 25 %. Significant level of intracellular reactive oxygen species (ROS) generation was estimated through fluorescence probe DCF-H2. Increased apoptotic cells were evident through AO/EB staining and phosphatidyl serine translocation in cell membrane. Single-stranded DNA damage was marked through single-cell gel electrophoresis. Mitochondrial membrane depolarization and lysosomal destabilization were evident. Upregulation of Bax and p21 and downregulation of Bcl-2 genes and corresponding protein levels supported apoptotic cell death of keratinocyte cells. Cyclobutane pyrimidine dimers (CPDs) were confirmed through immunofluorescence. In addition, hallmarks of apoptosis and G2/M phase cell cycle arrest were confirmed through flow cytometry analysis. Our findings suggest that MQ may damage DNA and produce DNA lesions which may induce differential biological responses in the skin on brief exposure to UVB and sunlight.

Natural autophagy activators: A promising strategy for combating photoaging.

BACKGROUND: Photodamage to the skin stands out as one of the most widespread epidermal challenges globally. Prolonged exposure to sunlight containing ultraviolet radiation (UVR) instigates stress, thereby compromising the skin's functionality and culminating in photoaging. Recent investigations have shed light on the importance of autophagy in shielding the skin from photodamage. Despite the acknowledgment of numerous phytochemicals possessing photoprotective attributes, their potential to induce autophagy remains relatively unexplored. PURPOSE: Diminished autophagy activity in photoaged skin underscores the potential benefits of restoring autophagy through natural compounds to enhance photoprotection. Consequently, this study aims to highlight the role of natural compounds in safeguarding against photodamage and to assess their potential to induce autophagy via an in-silico approach. METHODS: A thorough search of the literature was done using several databases, including PUBMED, Science Direct, and Google Scholar, to gather relevant studies. Several keywords such as Phytochemical, Photoprotection, mTOR, Ultraviolet Radiation, Reactive oxygen species, Photoaging, and Autophagy were utilized to ensure thorough exploration. To assess the autophagy potential of phytochemicals through virtual screening, computational methodologies such as molecular docking were employed, utilizing tools like AutoDock Vina. Receptor preparation for docking was facilitated using MGLTools. RESULTS: The initiation of structural and functional deterioration in the skin due to ultraviolet radiation (UVR) or sunlight-induced reactive oxygen species/reactive nitrogen species (ROS/RNS) involves the modulation of various pathways. Natural compounds like phenolics, flavonoids, flavones, and anthocyanins, among others, possess chromophores capable of absorbing light, thereby offering photoprotection by modulating these pathways. In our molecular docking study, these phytochemicals have shown binding affinity with mTOR, a negative regulator of autophagy, indicating their potential as autophagy modulators. CONCLUSION: This integrated review underscores the photoprotective characteristics of natural compounds, while the in-silico analysis reveals their potential to modulate autophagy, which could significantly contribute to their anti-photoaging properties. The findings of this study hold promise for the advancement of cosmeceuticals and therapeutics containing natural compounds aimed at addressing photoaging and various skin-related diseases. By leveraging their dual benefits of photoprotection and autophagy modulation, these natural compounds offer a multifaceted approach to combatting skin aging and related conditions.

Involvement of type-1 pathway in phototoxicity of benzo[ghi]perylenean ingredient of tattoo ink at ambient exposure of UVR and sunlight.

Tattooing on different parts of the body is a very common fashion trend in all sections of society globally. Skin allergies and other related skin diseases are very common among tattoo users. Benzo[ghi]perylene (BP) is a PAH and an important component of tattoo ink that showed prominent absorption under ultraviolet radiation (UVR) region. Therefore, to provide safety to the skin, a thorough safety study of BP exposed under UVR and Sunlight is very essential to understand their hazardous impact on the skin. BP showed a strong absorption of UVA and UVB radiation of sunlight. It is photolabile and degraded under UVA, UVB, and Sunlight in progressing order of time (1-4 h) without generating any novel photoproducts. Further, BP showed a specific generation of O2.- and OH radicals via activation of type I photodynamic reaction under exposure to UVA, UVB and Sunlight. Photocytotoxicity results illustrated concentration-dependent cell viability reduction in all exposure conditions of UVA, UVB, and Sunlight, respectively. Fluorescent probes (2',7'-dichlorofluorescein diacetate and dihydroethidium) for intracellular reactive oxygen species (ROS) generation supported the involvement of ROS in the phototoxicity of BP in the HaCaT cell line. Hoechst staining showed significant genomic insult induced by BP under UVA and UVB. Photoexcited BP promoted cell cycle arrest in the G1 phase and induced apoptosis confirmed via acridine orange/ethidium bromide staining. The findings of gene expression also supported apoptotic cell death in photoexcited BP via an increase in the level of pro-apoptotic gene (Bax) and a decrease in the level of anti-apoptotic gene (Bcl-2). The aforementioned finding indicates that tattoo users should avoid using BP since it can cause skin damage/diseases if they are exposed to UVR or Sunlight while tattooing on the body.

Benzo(ghi)perylene (BgP) a black tattoo ingredient induced skin toxicity via direct and indirect mode of DNA damage under UVA irradiation.

Tattooing is a very common fashion trend across all the ages and gender of the society worldwide. Although skin inflammatory diseases are very frequent among tattoo users because of the active chemical ingredients used in tattoo ink, yet no ingredient-specific toxicity study has been performed. Benzo(ghi)perylene (BgP) is one of the PAHs and an important ingredient of black tattoo ink that shows strong absorption in UVA and UVB radiation of sunlight. Therefore, understanding the hazardous potential of BgP especially under UVA exposure is important for the safety of skin of tattoo users by considering the fact that penetration of UVA is in the dermis region where tattoo ingredients reside. To evaluate the hazardous potential of BgP on human skin under UVA exposure, different experimental tools i.e., in-chemico, in-silico and in-vitro were utilized. Our results illustrated that BgP photosensitized under UVA (1.5 mW/cm2) irradiation shows a degradation pattern till 4 h exposure. Photosensitized BgP reduced significant cell viability (%) at 1 µg/ml concentration. However, the pretreatment of singlet and hydroxyl radical quenchers, restoration of cell viability observed, confirmed the role of type-I and type-II photodynamic reactions in phototoxicity of BgP. Further, intracellular uptake of BgP in HaCaT cells was estimated and confirmed by UHPLC analysis. Molecular docking of BgP with DNA and formation of γ-H2AX foci demonstrated the DNA intercalation and double-stranded DNA damaging potential of BgP. Furthermore, acridine orange and ethidium bromide (AO/EB) dual staining showed apoptotic cell death via photosensitized BgP under UVA irradiation. The above findings suggest that BgP reached the human skin cell and induced dermal toxicity via direct and indirect mode of DNA damage under UVA exposure finally promoting the skin cell death. Thus, BgP-containing tattoo ink may be hazardous and may induce skin damage and diseases, especially in presence of UVA radiation of sunlight. To minimize the risk of skin diseases from synthetic ingredients in tattoo ink, the study highlights the importance of developing eco-friendly and skin-friendly tattoo ingredients by companies.

Involvement of Type-I and Type-II Photodynamic Reactions in Photosensitization of Fragrance Ingredient 2-acetonaphthone.

2-Acetonaphthone (2-ACN) is a synthetic fragrance material used in various cosmetics as an adulterant. Due to its frequent use, we have conducted an in-depth study to understand the photosensitizing potential of 2-ACN. Results of this study illustrate that 2-ACN showed photodegradation in 4 h under ambient UV radiation (UVR) and sunlight exposure. It generated (1-25 µg mL-1 ) superoxide anion radical (O2 ·- ) and singlet oxygen (1 O2 ) in the presence of UVR/sunlight through in chemico and in vitro test systems. 2-ACN (10 µg mL-1 ) showed a 43.9% and 57.4% reduction in cell viability under UVA and sunlight, respectively. Photosensitized 2-ACN generated intracellular reactive oxygen species (ROS) (6-folds in UVA and 8-folds in sunlight), which compromises the endoplasmic reticulum and mitochondrial membrane potential leading to cell death. Acridine orange/ethidium bromide dual staining and annexin-V/PI uptake showed cell death caused via 2-ACN under UVR exposure. The above findings signify the role of ROS via Type-I and Type-II photodynamic pathways in photosensitization of 2-ACN that ultimately promotes photodamage of important cellular organelles leading to cell death. The study advocates that solar radiation should be avoided by the users after the application of cosmetic products containing 2-ACN.

UVR-induced phototoxicity mechanism of methyl N-methylanthranilate in human keratinocyte cell line.

Fragrances are used in almost every cosmetic product. International Fragrance Association (IFRA) is the regulatory body that controls the use of fragrances in cosmetic products. Methyl-N-methylanthranilate (DMA) is a naturally derived fragrance, commonly used in cosmetic products such as fine perfumes, skin care products, etc. But there is a lack of detailed study in terms of its phototoxic and photogenotoxicity mechanisms under UVA/sunlight exposure. In this study, we have shown that DMA photodegrades in 4 h under UVA (1.5 mW/cm2) and sunlight. DMA (0.0001%-0.0025%) significantly reduced the cell viability as demonstrated by NRU and MTT assays in a dose-dependent manner under UVA (5.4 J/cm2) and sunlight (1 h) exposure in the HaCaT cell line. It generated excessive intracellular ROS (superoxide anion radical via type-I photodynamic reaction), resulting in lysosomal destabilization and mitochondrial membrane depolarization. Photo-activated DMA caused DNA fragmentation as observed by olive tail moment. DNA double-strand breaks was demonstrated by phosphorylation of H2AX-histone protein and formation of photo-micronuclei in skin keratinocytes. Additionally, photo-activated DMA upregulated the oxidative stress marker gene hemeoxygenase-1 and apoptotic marker genes (cytochrome-C, caspase-3, caspase-9). Activated caspase-cascade pathway established that photo-activated DMA can potentially trigger apoptosis in the human skin cells.

Superoxide anion radical induced phototoxicity of 2,4,5,6-Tetraminopyrimidine sulfate via mitochondrial-mediated apoptosis in human skin keratinocytes at ambient UVR exposure.

2,4,5,6-Tetraaminopyrimidine sulfate (TAPS) is worldwide the most commonly used developer in hair dyes. As skin is the major organ, which is directly exposed to these permanent hair dyes, a comprehensive dermal safety assessment is needed. Hereto, we studied the photosensitization potential and mechanism involved in dermal phototoxicity of TAPS exposed to the dark and UVA/UVB/Sunlight by using different in-chemico and mammalian (HaCaT) cells, as test systems. Our experimental outcomes illustrate that TAPS get photodegraded (LC-MS/MS) and specifically generated superoxide anion radical (O2•-) under UVA and UVB via type-I photodynamic reaction. The phototoxic potential of TAPS is measured through MTT, NRU, and LDH assays that depicted a significant cell viability reduction at 25 µg/ml concentration and higher. Different cellular stainings (PI uptake, AO/EB, JC-1, NR uptake) suggested the role of mitochondrial-mediated apoptosis. Further, the transcriptomics study revealed upregulation of Apaf-1, Bax, Cytochrome c, Caspase 3, Caspase 9 and downregulation of Catalase and Bcl-2 by TAPS treated cells that strengthen our findings. Thus, the above findings suggest that chronic application of TAPS may be hazardous for human skin and promote various skin diseases.

Resveratrol enhances ultraviolet B-induced cell death through nuclear factor-kappaB pathway in human epidermoid carcinoma A431 cells.

Resveratrol has been reported to suppress cancer progression in several in vivo and in vitro models, whereas ultraviolet B (UVB), a major risk for skin cancer, is known to induce cell death in cancerous cells. Here, we investigated whether resveratrol can sensitize A431 human epidermoid carcinoma cells to UVB-induced cell death. We examined the combined effect of UVB (30 mJ/cm(2)) and resveratrol (60 microM) on A431 cells. Exposure of A431 carcinoma cells to UVB radiation or resveratrol can inhibit cell proliferation and induce apoptosis. However, the combination of resveratrol and UVB exposure was associated with increased proliferation inhibition of A431 cells compared with either agent alone. Furthermore, results showed that resveratrol and UVB treatment of A431 cells disrupted the nuclear factor-kappaB (NF-kappaB) pathway by blocking phosphorylation of serine 536 and inactivating NF-kappaB and subsequent degradation of IkappaBalpha, which regulates the expression of survivin. Resveratrol and UVB treatment also decreased the phosphorylation of tyrosine 701 of the important transcription factor signal transducer activator of transcription (STAT1), which in turn inhibited translocation of phospho-STAT1 to the nucleus. Moreover, resveratrol/UVB also inhibited the metastatic protein LIMK1, which reduced the motility of A431 cells. In conclusion, our study demonstrates that the combination of resveratrol and UVB act synergistically against skin cancer cells. Thus, resveratrol is a potential chemotherapeutic agent against skin carcinogenesis.

Correction to: Inhibitory Effects of Bisphenol-A on Neural Stem Cells Proliferation and Differentiation in the Rat Brain Are Dependent on Wnt/ß-Catenin Pathway.

The original version of this article unfortunately contained a mistake.