<%@ Page Language="C#" AutoEventWireup="true" CodeBehind="article.aspx.cs" Inherits="SPFWeb.article" %> <%@ Register Assembly="AjaxControlToolkit" Namespace="AjaxControlToolkit" TagPrefix="asp" %> Limitless Coverage - Innovations in SPF
clinical studies

Caffeine and caffeine sodium benzoate have a sunscreen effect, enhance UVB-induced apoptosis, and inhibit UVB-induced skin carcinogenesis in SKH-1 mice.
Lu YP, Lou YR, Xie JG, Peng QY, Zhou S, Lin Y, Shih WJ, Conney AH.

Carcinogenesis. 2007 Jan;28(1):199-206.

Abstract
Topical application of caffeine sodium benzoate (caffeine-SB) immediately after UVB irradiation of SKH-1 mice enhanced UVB-induced apoptosis by a 2- to 3-fold greater extent than occurred after the topical application of an equimolar amount of caffeine. Although topical application of caffeine-SB or caffeine enhanced UVB-induced apoptosis, both substances were inactive on non-UVB-treated normal skin. Topical application of caffeine-SB or caffeine (each has UVB absorption properties) 0.5 h before irradiation with a high dose of UVB decreased UVB-induced thymine dimer formation and sunburn lesions (sunscreen effect). Caffeine-SB was more active than an equimolar amount of caffeine in exerting a sunscreen effect. In additional studies, caffeine-SB strongly inhibited the formation of tumors in UVB-pretreated 'high-risk mice' and in tumor-bearing mice, and the growth of UVB-induced tumors was also inhibited. Caffeine-SB and caffeine are the first examples of compounds that have both a sunscreen effect and enhance UVB-induced apoptosis. Our studies suggest that caffeine-SB and caffeine may be good agents for inhibiting the formation of sunlight-induced skin cancer.


http://www.ncbi.nlm.nih.gov/pubmed


ATR-Chk1 pathway inhibition promotes apoptosis after UV treatment in primary human keratinocytes: potential basis for the UV protective effects of caffeine.
Heffernan TP, Kawasumi M, Blasina A, Anderes K, Conney AH, Nghiem P.

J Invest Dermatol. 2009 Jul;129(7):1805-15. Epub 2009 Feb 26.

Abstract
New approaches to prevent and reverse UV damage are needed to combat rising sunlight-induced skin cancer rates. Mouse studies have shown that oral or topical caffeine promotes elimination of UV-damaged keratinocytes through apoptosis and markedly inhibits subsequent skin cancer development. This potentially important therapeutic effect has not been studied in human skin cells. Here, we use primary human keratinocytes to examine which of several caffeine effects mediates this process. In these cells, caffeine more than doubled apoptosis after 75 mJ cm(-2) of ultraviolet light B (UVB). Selectively targeting two of caffeine's known effects did not alter UVB-induced apoptosis: inhibition of ataxia-telangiectasia mutated and augmentation of cyclic AMP levels. In contrast, siRNA against ataxia-telangiectasia and Rad3-related (ATR) doubled apoptosis after UV through a p53-independent mechanism. Caffeine did not further augment apoptosis after UVB in cells in which ATR had been specifically depleted, suggesting that a key target of caffeine in this effect is ATR. Inhibition of a central ATR target, checkpoint kinase 1 (Chk1), through siRNA or a new and highly specific inhibitor (PF610666) also augmented UVB-induced apoptosis. These data suggest that a relevant target of caffeine is the ATR-Chk1 pathway and that inhibiting ATR or Chk1 might have promise in preventing or reversing UV damage.


http://www.ncbi.nlm.nih.gov/pubmed


Silymarin and skin cancer prevention: anti-inflammatory, antioxidant and immunomodulatory effects.
Katiyar SK.

Int J Oncol. 2005 Jan;26(1):169-76.

Abstract
Several environmental and genetic factors are involved in skin cancer induction, however exposure to chemical carcinogens and solar ultraviolet (UV) radiation are primarily responsible for several skin diseases including skin cancer. Chronic exposure of solar UV radiation to the skin leads to basal cell and squamous cell carcinoma, and melanoma. Chemoprevention of skin cancer by consumption of naturally occurring botanicals appears a practical approach and therefore world-wide interest is considerably increasing to use these botanicals. Sunscreens are useful but their protection is not ideal because of inadequate use, incomplete spectral protection and toxicity. Silymarin, a plant flavonoid isolated from the seeds of milk thistle (Silybum marianum), has been shown to have chemopreventive effects against chemical carcinogenesis as well as photocarcinogenesis in various animal tumor models. Topical treatment of silymarin inhibited 7,12-dimethylbenz(a)anthracene-initiated and several tumor promoters, like 12-O-tetradecanoylphorbol-13-acetate, mezerein, benzoyal peroxide and okadaic acid, induced skin carcinogenesis in mouse models. Similarly, silymarin also prevented UVB-induced skin carcinogenesis. Wide range of in vivo mechanistic studies indicated that silymarin possesses antioxidant, anti-inflammatory and immunomodulatory properties which may lead to the prevention of skin cancer in in vivo animal models. The available experimental information suggests that silymarin is a promising chemopreventive and pharmacologically safe agent which can be exploited or tested against skin cancer in human system. Moreover, silymarin may favorably supplement sunscreen protection and provide additional anti-photocarcinogenic protection.


http://www.ncbi.nlm.nih.gov/pubmed


Molecular mechanisms of inhibition of photocarcinogenesis by silymarin, a phytochemical from milk thistle (Silybum marianum L. Gaertn.).
Vaid M, Katiyar SK.

Int J Oncol. 2010 May;36(5):1053-60.

Abstract
Changes in life style over the past several decades including much of the time spent outdoors and the use of tanning devices for cosmetic purposes by individuals have led to an increase in the incidence of solar ultraviolet (UV) radiation-induced skin diseases including the risk of skin cancers. Solar UV radiations are considered as the most prevalent environmental carcinogens, and chronic exposure of the skin to UV leads to squamous and basal cell carcinoma and melanoma in human population. A wide variety of phytochemicals have been reported to have substantial anti-carcinogenic activity because of their antioxidant and anti-inflammatory properties. Silymarin is one of them and extensively studied for its skin photoprotective capabilities. Silymarin, a flavanolignan, is extracted from the fruits and seeds of milk thistle (Silybum marianum L. Gaertn.), and has been shown to have chemopreventive effects against photocarcinogenesis in mouse tumor models. Topical treatment of silymarin inhibited photocarcinogenesis in mice in terms of tumor incidence, tumor multiplicity and growth of the tumors. Wide range of in vivo mechanistic studies conducted in a variety of mouse models indicated that silymarin has anti-oxidant, anti-inflammatory and immunomodulatory properties which led to the prevention of photocarcinogenesis in mice. This review summarizes and updates the photoprotective potential of silymarin with the particular emphasis on its in vivo mechanism of actions. It is suggested that silymarin may favorably supplement sunscreen protection, and may be useful for skin diseases associated with solar UV radiation-induced inflammation, oxidative stress and immunomodulatory effects.


http://www.ncbi.nlm.nih.gov/pubmed