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

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.

Figure 1

Schematic representation of UV radiation-induced multi-stage skin carcinogenesis, showing initiation, promotion and progression stages. In the initiation stage genetic changes occurs in the cells. At the promotion stage, additional UV irradiation leads to the clonal expansion of initiated cells. Tumor progression stage involves the transformation of the benign tumor into an invasive and potentially metastatic malignant tumor. Silymarin can reverse, inhibit or retard the process of skin carcinogenesis at one or at all the stages of carcinogenesis.

Figure 2

Chemical structure of silibinin, the major and most biological active component of silymarin.

Figure 3

Molecular mechanisms and targets of silymarin in prevention of photocarcinogenesis. Upward arrows (↑) indicate the enhancement or stimulation and downward arrows (↓) indicates inhibition or downregulation of target molecules.