Silibinin and non-melanoma skin cancers

Abstract

Skin is the largest human organ that shields the inner body from contact with xenobiotic and genotoxic agents, and in this process, the skin's cellular genome faces continuous stress due to direct exposure to these noxious factors. Accumulation of genetic stress results in genomic alterations leading to undesirable gene or protein alteration/expression in skin cells, which eventually causes the formation of non-melanoma skin cancers (NMSCs). Ultraviolet B (UVB) radiation from sun is the most prominent factor contributing to ∼5 million skin cancer cases (which are mostly NMSCs) in the United States (US) and western countries. UVB exposure causes aberrations in a range of biochemical and molecular pathways such as: thymine dimer formation, DNA damage, oxidative stress, inflammatory responses, altered cellular signaling, which ultimately contribute to the development of NMSCs. The focus of this review is to summarize the protective and preventive potential of silymarin and/or silibinin against UVB-induced NMSC in pre-clinical skin cancer studies. Over two decades of research has shown the strong potential of silibinin, a biologically active flavonolignan (crude form Silymarin) derived from milk thistle plant, against a wide range of cancers, including NMSCs. Silibinin protects against UVB-induced thymine dimer formation and in turn promotes DNA repair and/or initiates apoptosis in damaged cells via an increase in p53 levels. Additionally, silibinin has shown strong efficacy against NMSCs via its potential to target aberrant signaling pathways, and induction of anti-inflammatory responses. Overall, completed comprehensive studies suggest the potential use of silibinin to prevent and/or manage NMSCs in humans.

Keywords: Basal cell carcinoma; Cyclobutane pyrimidine dimers; Hedgehog pathway; Photocarcinogenesis; Squamous cell carcinoma.

Graphical abstract

Fig. 1

Description of sequential steps in carcinogenesis process during non-melanoma skin cancer (SCC and BCC) development and progression after UVR exposure.

Fig. 2

Sequential steps in the biosynthesis of silymarin components including silibinin from Milk Thistle plant (Silybum marianum).

Fig. 3

Description of various DNA damage events during solar-UVB radiation induced epidermal skin DNA damage/photocarcinogenesis, eventually leading to skin tumor (NMSC) development via inducing gene/protein alterations, and activation of aberrant cellular signaling pathways.

Fig. 4

Scheme of different aberrant cellular signaling pathways associated with survival, apoptosis, inflammation, and oxidative stress (induced by UVR-exposure) which are targeted (increased or decreased) by silibinin treatment during prevention/intervention of skin NMSC growth and progression.