The Beneficial Effect of Rosmarinic Acid on Benzophenone-3-Induced Alterations in Human Skin Fibroblasts

Benzophenone-3 (BP-3) is one of the most widely used chemical sunscreens. The results of many in vitro and in vivo tests confirm its high percutaneous penetration and systemic absorption, which question the safety of its wide use. The aim of our research was to assess the effect of this compound on components of the skin extracellular matrix, and to investigate whether rosmarinic acid (RA) could reduce BP-3-induced changes in human skin fibroblasts. BP-3 used at concentrations of 0.1–100 µM caused a number of unfavorable changes in the level of type I collagen, decorin, sulfated glycosaminoglycans, hyaluronic acid, elastin, and expression or activity of matrix metalloproteinases (MMP-1, MMP-2), elastase and hyaluronidase. Moreover, the intracellular retention of collagen was accompanied by changes in the expression of proteins modifying and controlling the synthesis and secretion of this protein. Most importantly, RA at a concentration of 100 µM significantly reduced or completely abolished the adverse effects of BP-3. Based on these findings, it can be concluded that this polyphenol may provide effective protection against BP-3-induced disturbances in skin cells, which may have important clinical implications.

Chemical Composition and Protective Effect of Young Barley (Hordeum vulgare L.) Dietary Supplements Extracts on UV-Treated Human Skin Fibroblasts in In Vitro Studies

Young barley seems to be a promising material for use as nutricosmetic due to the presence of many biologically active compounds. The aim of this study was to evaluate the effect of Hordeum vulgare L. extracts on human skin fibroblasts exposed to ultraviolet radiation B (UVB) radiation. Analysis of the chemical composition showed a predominance of 9,12,15-octadecatrienoic acid. The quality assessment showed that young barley preparations have high total polyphenolic content (TPC) and favourable total antioxidant status (TAS). They also contain antioxidant elements such as zinc, copper, and selenium. Furthermore, the analyzed products were found to be safe in terms of toxic elements (lead, cadmium and mercury) and lack of cytotoxic effect of young barley extracts on cells. In vitro bioactivity assays showed that young barley extract increased the survival rate and accelerated the migration of fibroblasts in research models with UVB radiation. The application of both extracts caused an increase in DNA biosynthesis, and in the number of cells arrested in S phase. Moreover, an inhibitory effect of the tested extracts on the expression of matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9) was observed. The results indicate that young barley extracts, due to protective as well as restorative effect, could potentially be used in the production of nutricosmetics and skin care products.

Urea-functionalized organoselenium compounds as promising anti-HepG2 and apoptosis-inducing agents

Hepatocellular carcinoma is a highly aggressive and difficult-to-treat type of cancer. Incorporating urea functionality into the backbone of organoselenium compounds is expected to develop promising chemotherapeutic leads against liver cancer. Methods: Urea-functionalized organoselenium compounds were synthesized in good yields, and their cytotoxicity was evaluated against HepG2 cells. Results: 1,1′-(Diselanediylbis(4,1-phenylene))bis(3-phenylurea) (14) exhibited efficient anti-HepG2 activity in sub-micromolar concentrations, with no toxicity to normal human skin fibroblasts. The molecular mechanisms of the diselenide-based urea 14 were evaluated using colony formation, wound healing, 3D spheroid invasion assays, cell cycle analysis and apoptosis induction. Its redox properties were also assessed by using different bioassays. Conclusion: Our study revealed promising anticancer, antimigratory and anti-invasiveness properties of 1,1′-(diselanediylbis(4,1-phenylene))bis(3-phenylurea) (14) against HepG2.

Identification of genetic predispositions related to ionizing radiation in primary human skin fibroblasts from survivors of childhood and second primary cancer as well as cancer-free controls: Protocol for the nested case-control study KiKme. (Preprint)

BACKGROUND Therapy of a first primary neoplasm (FPN) in childhood with high doses of ionizing radiation is an established risk factor for second primary neoplasms (SPN). An association between exposure to low doses and childhood cancer is also suggested, however, results are inconsistent. As only subgroups of children with FPNs develop SPNs, an interaction between radiation, genetic, and other risk factors is presumed to influence cancer development. OBJECTIVE Therefore, the population-based nested case-control study KiKme aims to identify differences in genetic predispositions and radiation-response between childhood cancer survivors with and without SPNs as well as cancer-free controls. METHODS We conducted a population-based nested case-control study KiKme. Besides questionnaire information, skin biopsies and saliva samples are available. By measuring individual reactions to different exposures of radiation (e.g., 0.05 and 2 Gray) in normal somatic cells of the same person, our design enables us to create several exposure scenarios for the same person simultaneously and measure several different molecular markers (e.g., deoxyribonucleic acid (DNA), messenger RNA, long non-coding RNA, copy number variation). RESULTS Since 2013, 101 out of 247 invited SPN patients, 340 out of 1,729 invited FPN patients, and 150 out of 246 invited cancer-free controls were recruited and matched by age and sex. Childhood cancer patients were additionally matched by tumor morphology, year of, and age at diagnosis. Participants reported on lifestyle, socio-economical and anthropometric factors, as well as on medical radiation history, health, and family history of diseases (N = 556). Primary human fibroblasts from skin biopsies of the participants were cultivated (N = 499) and cryopreserved (N = 3,886). DNA was extracted from fibroblasts (N = 488) and saliva (N = 510). CONCLUSIONS This molecular-epidemiological study is the first to combine observational epidemiological research with standardized experimental components in primary human skin fibroblasts to identify genetic predispositions related to ionizing radiation in childhood and SPNs. In the future, fibroblasts of the participants will be used for standardized irradiation experiments, which will inform analysis of the case-control study and vice versa. Differences between participants will be identified using several molecular markers. With its innovative combination of experimental and observational components, this new study will provide valuable data to forward research on radiation-related risk factors in childhood cancer and SPNs.