UV-induced immune suppression and photocarcinogenesis: chemoprevention by dietary botanical agents

Abstract

Studies of immune-suppressed transplant recipients and patients with biopsy-proven skin cancer have confirmed that ultraviolet (UV) radiation-induced immune suppression is a risk factor for the development of skin cancer in humans. UV radiation suppresses the immune system in several ways. The UVB spectrum inhibits antigen presentation, induces the release of immunosuppressive cytokines, and elicits DNA damage that is a molecular trigger of UV-mediated immunosuppression. It is therefore important to elucidate the mechanisms underlying UV-induced immunosuppression as a basis for developing strategies to protect individuals from this effect and subsequent development of skin cancer. Dietary botanicals are of particular interest as they have been shown to inhibit UV-induced immune suppression and photocarcinogenesis. In this review, we summarize the most recent investigations and mechanistic studies regarding the photoprotective efficacy of selected dietary agents, including, green tea polyphenols, grape seed proanthocyanidins and silymarin. We present evidence that these chemopreventive agents prevent UVB-induced immunosuppression and photocarcinogenesis through: (i) the induction of immunoregulatory cytokine interleukin (IL)-12; (ii) IL-12-dependent DNA repair; and (iii) stimulation of cytotoxic T cells in the tumor microenvironment. The new information regarding the mechanisms of action of these agents supports their potential use as adjuncts in the prevention of photocarcinogenesis.

Figure 1

Molecular and cellular targets in the skin that are affected by UV radiation resulting in induction of immune suppression. Upward arrows (↑) indicate the enhancement or stimulation.

Figure 2

Dietary agents (GTPs, GSPs and silymarin) have the ability to block the adverse biological effects of UV radiation through the induction of the immunoregulatory cytokine, IL-12, thus preventing UV-induced immune suppression. Inhibition of UV-induced immune suppression contributes to the prevention of photocarcinogenesis. Upward arrows (↑) indicate the enhancement or stimulation.