The effects of sun exposure on the skin and specifically those related to pigmentation disorders are well known. It has recently been shown that blue light leads to the induction of oxidative stress and long-lasting pigmentation. The protective effect of an aqueous extract of Polypodium leucotomos (Fernblock®) is known. Our aim was to investigate the action mechanism of Fernblock® against pigmentation induced by blue light from digital devices. Human fibroblasts (HDF) and murine melanocytes (B16-F10) were exposed to artificial blue light (a 400–500 nm LED lamp). Cell viability, mitochondrial morphology, and the expression of the mitogen-activated protein kinase (MAPK) p38, known markers involved in the melanogenesis pathway, were evaluated. The activation of Opsin-3, a membrane protein sensitive to blue light that triggers the activation of the enzyme tyrosinase responsible for melanogenesis in melanocytes, was also analyzed. Our results demonstrated that pretreatment with Fernblock® prevents cell death, alteration of mitochondrial morphology, and phosphorylation of p38 in HDF exposed to blue light. In addition, Fernblock® significantly reduced the activation of Opsin-3 in melanocytes and the photo-oxidation of melanin, preventing its photodegradation. In sum, Fernblock® exerts beneficial effects against the detrimental impact of blue light from digital devices and could prevent early photoaging, while maintaining skin homeostasis.
As an important component of tumor microenvironment, cancer-associated fibroblasts (CAFs) have lately gained prominence owing to their crucial role in the resistance to therapies. Photodynamic therapy (PDT) stands out as a successful therapeutic strategy to treat cutaneous squamous cell carcinoma. In this study, we demonstrate that the transforming growth factor β1 (TGFβ1) cytokine secreted by CAFs isolated from patients with SCC can drive resistance to PDT in epithelial SCC cells. To this end, CAFs obtained from patients with in situ cSCC were firstly characterized based on the expression levels of paramount markers as well as the levels of TGFβ1 secreted to the extracellular environment. On a step forward, two established human cSCC cell lines (A431 and SCC13) were pre-treated with conditioned medium obtained from the selected CAF cultures. The CAF-derived conditioned medium effectively induced resistance to PDT in A431 cells through a reduction in the cell proliferation rate. This resistance effect was recapitulated by treating with recombinant TGFβ1 and abolished by using the SB525334 TGFβ1 receptor inhibitor, providing robust evidence of the role of TGFβ1 secreted by CAFs in the development of resistance to PDT in this cell line. Conversely, higher levels of recombinant TGFβ1 were needed to reduce cell proliferation in SCC13 cells, and no induction of resistance to PDT was observed in this cell line in response to CAF-derived conditioned medium. Interestingly, we probed that the comparatively higher intrinsic resistance to PDT of SCC13 cells was mediated by the elevated levels of TGFβ1 secreted by this cell line. Our results point at this feature as a promising biomarker to predict both the suitability of PDT and the chances to optimize the treatment by targeting CAF-derived TGFβ1 in the road to a more personalized treatment of particular cSCC tumors.
Exposure to sun and especially to ultraviolet radiation (UVR) exerts well known detrimental effects on skin which are implicated in malignancy. UVR induces production of cyclobutane pyrimidine dimers (CPDs), immediately during exposure and even hours after the exposure, these latter being called dark-CPDs, as consequence of the effects of different reactive species that are formed. Fernblock® (FB), an aqueous extract of Polypodium leucotomos, has proven to have photoprotective and antioxidant effects on skin. The aim of our work was to investigate the potential photoprotective effect of FB against dark-CPD formation. Murine melanocytes (B16-F10) were exposed to UVA radiation and the production of dark-CPDs and different reactive oxygen and nitrogen species (ROS and RNS) was measured. Significant dark-CPD formation could be seen at 3h after UVA irradiation, which was inhibited by the pre-treatment of cells with FB. Formation of nitric oxide, superoxide and peroxynitrite was increased after irradiation, consistent with the increased CPD formation. FB successfully reduced the production of these reactive species. Hence, these results show how dark-CPDs are formed in UVA irradiated melanocytes, and that FB acts as a potential antioxidant and ROS scavenger, preventing the DNA damage induced by sun exposure.
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