## 5 Vitamin D Health-Promoting Activities  
### Anti-Melanoma and Anti-Cancer Activities  
Melanoma is a cancerous condition during which melanocytes--the neutral crest-originated cells responsible for producing melanin (the pigment that gives skin its color)--undergo a transformation, becoming malignant [31; 37]. Ultraviolet radiation (UV\({}_{\text{R}}\)), chemical and biological mediators, including hormonal and non-hormonal regulators, and genetic and molecular modulators are examples of some factors that can regulate the melanogenic activity and action of melanocytes [143; 143]. The World Health Organization (WHO) classifies melanoma based on etiology, and more specifically whether it is connected to sun exposure or not, with the former stratified into low- and high-cumulative solar damage (CSD) of the skin. Examples non-related to sun exposure etiology are mucosal, acral, uveal, and Spitzoid melanomas; melanomas developing in blue or congenital nevi; and uncommon melanomas in the central nervous system (CNS) [144; 145].  
Melanoma is a lethal type of cancer, with a poor prognosis especially when the disease is spread to other body areas. One of the most common types of melanomas is cutaneous melanoma, which has a constantly increasing annual incident rate. Such a type mainly appears in older people, but it has been found in younger people as well. There are a few current treatment schemes, which are unfortunately expensive, and are followed by multiple side effects. Thus, the need for new treatment methods is vastly increasing [32].  
It is important to understand how vitamin D may regulate a variety of biological pathways. In more detail, responsible for both the genomic and non-genomic regulation of several biological processes is the binding of 1\(\alpha\),25(OH)\({}_{\text{2}}\)D\({}_{\text{3}}\) to the \(VDR\) in the target tissues. As widely accepted, the \(VDR\) belongs to the nuclear type of receptor family, which contains ligand-activated transcription factors, and nearly all tissues and cells, including skin cells, are able to express it. According to [PERSON] et al. [146], their research indicated that there is an inverse relationship between melanoma progression and \(VDR\) expression, proposing that \(VDR\) may function as a gene that suppresses melanoma tumors [146]. It is generally acknowledged that vitamin D compounds hold great promise for both the prevention and treatment of cancer, due to their antiproliferative properties towards specific cancer types, predominantly by promoting differentiation and suppressing proliferation [147].  
This observation has been confirmed by results deriving from clinical trials on different melanoma types and by epidemiological and preclinical evidence [32; 148]. Moreover, both molecular and clinicopathological studies have pointed out a connection between vitamin D signaling abnormalities and the development and the possible outcome of melanoma. As a consequence, successful treatment for melanoma may involve sufficient vitamin D signaling and vitamin D-based interventions [32].  
According to [PERSON] et al. [147], in the human melanoma cell lines used in the investigation, 1\(\alpha\),25(OH)\({}_{2}\)D\({}_{3}\) dramatically decreased cell viability and raised caspase levels. Usually during melanoma, the phosphatase and tensin homologue (PTEN), which is a tumor suppressor, is mutated. In this study, results showed an increase in the PTEN levels and a reported downregulation of both the protein kinase B (AKT) pathway and its downstream effectors. Thus, 1\(\alpha\),25(OH)\({}_{2}\)D\({}_{3}\) is a potent factor able to efficiently target PTEN and to reduce melanoma cell viability [147].