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Resveratrol, a polyphenolic phytoalexin, is a very effective antioxidant that also exhibits strong antiproliferative and anti-inflammatory properties. Recent studies have provided support for the use of resveratrol in human cancer chemoprevention, in combination with either chemotherapeutic drugs or cytotoxic factors for a most efficient treatment of drug refractory tumor cells. Resveratrol is also widely used in topical preparations, as a chemoprotective compound against development of several cutaneous disorders, including skin cancer. Nevertheless, the combined effect of resveratrol and UVA irradiation on cellular toxicity and DNA damage has never been assessed. The aim of this work was to investigate the effect of resveratrol on cell fate in immortalized human keratinocytes HaCaT cells. The results indicated that resveratrol potentiates the production of significant amounts of 8-oxo-7,8-dihydro-2- deoxyguanosine in UVA-irradiated genomic DNA. Moreover, the combination of resveratrol with UVA significantly enhances the induction of DNA strand breaks and cell death in HaCaT keratinocytes. The conclusion is a potential hazardous effect of topical application of resveratrol, particularly on regions exposed to sunlight.

Zinc is an essential trace element for life. Zinc is not only an important nutrient, cofactor of numerous enzymes and transcription factors, but also it acts as an intracellular mediator, similarly to calcium. The recent discovery of its intracellular molecular pathways opens the door to new fields of drug design. Zinc homeostasis results from a coordinated regulation by different proteins involved in uptake, excretion and intracellular storage / trafficking of zinc. These proteins are membranous transporters, belonging to the ZIP and ZnT families, and metallothioneins. Their principal function is to provide zinc to new synthesized proteins, important for several functions such as gene expression, immunity, reproduction or protection against free radicals damage. Zinc intracellular concentration is correlated to cell fate, ie proliferation, differentiation or apoptosis, and modifications of zinc homeostasis are observed in several pathologies affecting humans at any stage of life. Two zinc-related diseases, acrodermatitis enteropathica and the lethal milk syndrome, have been recently related to mutations in zinc transporters, SLC39A4 and ZnT-4, respectively. Zinc acts as an inhibitor of apoptosis, while its depletion induces programmed cell death in many cell lines. However, excess zinc can also be cytotoxic, and zinc transporters as well as metallothioneins serve as zinc detoxificating systems. Several zinc channels, controlling the intracellular zinc movements and the free form of the metal, maintain the intracellular zinc homeostasis, and thus the balance between life and cell death. Apart from these general activities, zinc has particular biological roles in some specialized cells. It acts as a paracrine regulator in pancreatic cell, neuron or neutrophil activity by a mechanism of vesicles-mediated metal excretion and uptake. A well knowledge on zinc transporters will be useful to develop new molecular targets to act on these zinc-regulated biological functions.