Melanoma induction by ultraviolet A but not ultraviolet B radiation requires melanin pigment

Malignant melanoma of the skin (CMM) is associated with ultraviolet radiation exposure, but the mechanisms and even the wavelengths responsible are unclear. Here we use a mammalian model to investigate melanoma formed in response to precise spectrally defined ultraviolet wavelengths and biologically relevant doses. We show that melanoma induction by ultraviolet A (320–400 nm) requires the presence of melanin pigment and is associated with oxidative DNA damage within melanocytes. In contrast, ultraviolet B radiation (280–320 nm) initiates melanoma in a pigment-independent manner associated with direct ultraviolet B DNA damage. Thus, we identified two ultraviolet wavelength-dependent pathways for the induction of CMM and describe an unexpected and significant role for melanin within the melanocyte in melanomagenesis

Dual Action of Curcumin as an Anti- and Pro-Oxidant from a Biophysical Perspective

Curcumin, a natural polyphenol widely used as a spice, colorant and food additive, has been shown to have therapeutic effects against different disorders, mostly due to its anti-oxidant properties. Curcumin also reduces the efficiency of melanin synthesis and affects cell membranes. However, curcumin can act as a pro-oxidant when blue light is applied, since upon illumination it can generate singlet oxygen. Our review aims to describe this dual role of curcumin from a biophysical perspective, bearing in mind its concentration, bioavailability-enhancing modifications and membrane interactions, as well as environmental conditions such as light. In low concentrations and without irradiation, curcumin shows positive effects and can be recommended as a beneficial food supplement. On the other hand, when used in excess or irradiated, curcumin can be toxic. Therefore, numerous attempts have been undertaken to test curcumin as a potential photosensitizer in photodynamic therapy (PDT). At that point, we underline that curcumin-based PDT is limited to the treatment of superficial tumors or skin and oral infections due to the weak penetration of blue light. Additionally, we conclude that an increase in curcumin bioavailability through the using nanocarriers, and therefore its concentration, as well as its topical use if skin is exposed to light, may be dangerous

A melanin-independent interaction between Mc1r and Met signaling pathways is required for HGF-dependent melanoma

Melanocortin 1 receptor (MC1R) signaling stimulates black eumelanin production through a cAMP dependent pathway. MC1R polymorphisms can impair this process, resulting in a predominance of red phaeomelanin. The red hair, fair skin and UV sensitive phenotype is a well-described melanoma risk factor. MC1R polymorphisms also confer melanoma risk independent of pigment. We investigated the effect of Mc1r deficiency in a mouse model of UV-induced melanoma. C57BL/6-Mc1r(+/+)-HGF transgenic mice have a characteristic hyperpigmented black phenotype with extra-follicular dermal melanocytes located at the dermal/epidermal junction. UVB induces melanoma, independent of melanin pigmentation, but UVA-induced and spontaneous melanomas are dependent on black eumelanin. We crossed these mice with yellow C57BL/6-Mc1r(e/e) animals which have a non-functional Mc1r and produce predominantly yellow phaeomelanin. Yellow C57BL/6-Mc1r(e/e)-HGF mice produced no melanoma in response to UVR or spontaneously even though the HGF transgene and its receptor Met were expressed. Total melanin was less than in C57BL/6-Mc1r(+/+)-HGF mice, hyperpigmentation was not observed and there were few extra-follicular melanocytes. Thus, functional Mc1r was required for expression of the transgenic HGF phenotype. Heterozygous C57BL/6-Mc1r(e/+)-HGF mice were black and hyperpigmented and, although extra-follicular melanocytes and skin melanin content were similar to C57BL/6-Mc1r(+/+)-HGF animals, they developed UV-induced and spontaneous melanomas with significantly less efficiency by all criteria. Thus, heterozygosity for Mc1r was sufficient to restore the transgenic HGF phenotype but insufficient to fully restore melanoma. We conclude that a previously unsuspected melanin-independent interaction between Mc1r and Met signaling pathways is required for HGF-dependent melanoma and postulate that this pathway is involved in human melanoma

Riboflavin and Its Derivates as Potential Photosensitizers in the Photodynamic Treatment of Skin Cancers

Riboflavin, a water-soluble vitamin B2, possesses unique biological and physicochemical properties. Its photosensitizing properties make it suitable for various biological applications, such as pathogen inactivation and photodynamic therapy. However, the effectiveness of riboflavin as a photosensitizer is hindered by its degradation upon exposure to light. The review aims to highlight the significance of riboflavin and its derivatives as potential photosensitizers for use in photodynamic therapy. Additionally, a concise overview of photodynamic therapy and utilization of blue light in dermatology is provided, as well as the photochemistry and photobiophysics of riboflavin and its derivatives. Particular emphasis is given to the latest findings on the use of acetylated 3-methyltetraacetyl-riboflavin derivative (3MeTARF) in photodynamic therapy