Ethinylestradiol and Levonorgestrel as Active Agents in Normal Skin, and Pathological Conditions Induced by UVB Exposure: In Vitro and In Ovo Assessments

Abstract

The link between melanoma development and the use of oral combined contraceptives is not fully elucidated, and the data concerning this issue are scarce and controversial. In the present study, we show that the components of oral contraceptives, ethinylestradiol (EE), levonorgestrel (LNG), and their combination (EE + LNG) ± UVB (ultraviolet B radiation) induced differential effects on healthy (human keratinocytes, fibroblasts, and primary epidermal melanocytes, and murine epidermis cells) and melanoma cells (human—A375 and murine—B164A5), as follows: (i) at low doses (1 µM), the hormones were devoid of significant toxicity on healthy cells, but in melanoma cells, they triggered cell death via apoptosis; (ii) higher doses (10 µM) were associated with cytotoxicity in all cells, the most affected being the melanoma cells; (iii) UVB irradiation proved to be toxic for all types of cells; (iv) UVB irradiation + hormonal stimulation led to a synergistic cytotoxicity in the case of human melanoma cells—A375 and improved viability rates of healthy and B164A5 cells. A weak irritant potential exerted by EE and EE + LNG (10 µM) was assessed by the means of a chick chorioallantoic membrane assay. Further studies are required to elucidate the hormones’ cell type-dependent antimelanoma effect and the role played by melanin in this context.

Melanin and Behaviour of Melanoma-related Cell Lines in the Presence of Ultraviolet B Type Radiation

“…Primary epidermal melanocytes (HEMa) have been taken in this study due to the major involvement of melanogenesis in the development of melanoma. It is also known that genetic factors and hormone status play a key role in regulating melanin synthesis [10]. One type of mechanism involved in the protection of melanocytes against UVB radiation or the development of malignant tumors involves the development of melanocytic dendrites as melanin pigment carriers from melanocytic cells to keratinocytes.…”

“…Cell viability was evaluated by the Alamar blue assay: 10,000 cells/200 µL medium/well were seeded in a 96well plate, incubated for 24h after UVB exposure and spectrophotometrically analysed at 570 nm and 600 nm wavelengths with a xMark™Microplate Spectrophotometer (BioRad) as previous described [10,11].…”

“…Melanin ( fig. 1) has a double action, namely: 1) beneficial -due to its protective role on melanocytes in the case of UVB and oxidative stress, and 2) harmful -due to possible degraded melanogenesis that is responsible for melanoma therapy resistance) [9,10].…”

“…In addition, specialty studies highlight the higher radiotherapy sensitivity of amelanotic melanomas compared to melanotic melanomas, also taking into account a higher survival rate for amelanotic ones [8,10].…”

Thyme Leaves Aqueous Extract and its Formulations. A comparative study based on chemical structures and biological activity

“…Regarding the activity of thyme extract and its biosynthesized particles with silver, T47D cells were stimulated with different concentrations of test compounds samples (concentrations between 12.5 -200µg/mL) in one study conducted by Heidari et al Their results showed that SilNPs affected the cell viability in a percentage of about 90% at the highest concentration of 200 µg/mL, while the thyme extract was less toxic on same cells [13,14].…”