Mechanisms of Photoaging and Cutaneous Photocarcinogenesis, and Photoprotective Strategies with Phytochemicals

Abstract

Photoaging and photocarcinogenesis are primarily due to solar ultraviolet (UV) radiation, which alters DNA, cellular antioxidant balance, signal transduction pathways, immunology, and the extracellular matrix (ECM). The DNA alterations include UV radiation induced thymine-thymine dimers and loss of tumor suppressor gene p53. UV radiation reduces cellular antioxidant status by generating reactive oxygen species (ROS), and the resultant oxidative stress alters signal transduction pathways such as the mitogen-activated protein kinase (MAPK), the nuclear factor-kappa beta (NF-κB)/p65, the janus kinase (JAK), signal transduction and activation of transcription (STAT) and the nuclear factor erythroid 2-related factor 2 (Nrf2). UV radiation induces pro-inflammatory genes and causes immunosuppression by depleting the number and activity of the epidermal Langerhans cells. Further, UV radiation remodels the ECM by increasing matrixmetalloproteinases (MMP) and reducing structural collagen and elastin. The photoprotective strategies to prevent/treat photoaging and photocarcinogenesis include oral or topical agents that act as sunscreens or counteract the effects of UV radiation on DNA, cellular antioxidant balance, signal transduction pathways, immunology and the ECM. Many of these agents are phytochemical derivatives and include polyphenols and non-polyphenols. The flavonoids are polyphenols and include catechins, isoflavones, proanthocyanidins, and anthocyanins, whereas the non-flavonoids comprise mono phenolic acids and stilbenes. The natural sources of polyphenols include tea, cocoa, grape/wine, soy, pomegranate, and Polypodium leucotomos. The non-phenolic phytochemicals include carotenoids, caffeine and sulphoraphance (SFN). In addition, there are other phytochemical derivatives or whole extracts such as baicalin, flavangenol, raspberry extract, and Photomorphe umbellata with photoprotective activity against UVB radiation, and thereby carcinogenesis.

The dark side of the light: mechanisms of photocarcinogenesis

“…32 Among these UV-induced mediators, the major player of immunosuppression appears to be IL-10, a T h2 cytokine. Released by UV-irradiated keratinocytes in response to the formation of CPDs or cis-UCA, 49 macrophages migrating into UV-irradiated skin, and UV-induced T reg , this cytokine acts on LCs, abrogating their ability to present antigens and inducing immunologic tolerance. 29,32 IL-10 enhances the proliferation of T reg , while suppressing T-cell-mediated defense mechanisms, facilitating the growth of UV-induced skin tumors.…”

The dark side of the light: Phototherapy adverse effects

“…As a result, photoprotective strategies using oral, or to a lesser extent topical, antioxidant agents, namely phytochemical derivatives, have gained increased attention for their potential anti-neoplastic properties (Table 2). [44][45][46][47] Such botanic antioxidants include polyphenols (flavonoids and non-flavonoids), non-phenolic derivatives, and whole plant extracts, which are present in various vegetables, fruits, beans, cereals, and beverages, such as tea, cocoa, and wine. These can also be found as concentrated dietary supplements and skin care products.…”

“…[44][45][46][47] Vitamin A and its derivatives are largely beneficial in preventing skin cancer (Table 2) because they promote differentiation, growth arrest, and apoptosis of epidermal keratinocytes. 31,45,48 Retinoids have actually been found effective in preventing NMSC in high-risk patients, namely those submitted to large doses of PUVA. 49 Associating these agents with phototherapy treatment regimens may have potential anti-cancer benefits in the long term.…”

Scenario for adequate cutaneous vitamin D 3 synthesis due to solar radiation in Poland for people with phototype II and III

“…World Health Organization -WHO) tego czynnika fizycznego na liście kancerogenów. Nadmierna ekspozycja na promieniowanie słoneczne wpływa na przyspieszone starzenie się skóry, rozwój nowotworów, a także na stan miejscowej odpowiedzi immunologicznej [5]. Wyniki prowadzonych badań stanowią racjonalną przesłankę do stosowania codziennej fotoprotekcji, jednak zalecenie unikania promieniowania słonecznego w godz.…”