Skin Cancer, Polyphenols, and Oxidative Stress

Abstract The characteristics of malignancy are cell growth and remodelling of the extracellular matrix for angiogenesis and metastasis. One of the major causes of skin cancer (melanoma and nonmelanoma) is the cellular accumulation reactive oxygen species (ROS), which outbalances the cellular antioxidant system, causing oxidative stress with intrinsic aging but more so with the exposure of skin to environmental pollutants and ultraviolet (UV) radiation. The ROS damage DNA, proteins, and lipids, and activate inflammatory cytokines that activate the signal transduction pathways of the mitogen activated protein kinase (MAPK), nuclear factor-kappa beta (NF-κB)/p65, and JAK/STAT (Signal Transduction and Activation of Transcription), which in turn activate factors such as activator-1 (AP-1) transcription factor. The activation of these pathways results in the increased expression of matrixmetalloproteinases (MMPs), Transforming Growth Factor-β (TGF-β), and Vascular Endothelial Growth Factor (VEGF), which collectively remodel the extracellular matrix (ECM) for tumor growth, angiogenesis, and metastasis. Polyphenols are effective in anticarcinogenesis largely because of their antioxidant and anti-inflammatory properties. Polyphenols include the classes of flavonoids, anthocyanins, catechins, lignans, proanthocyanidins, tannins, and more; and the hydroxyl groups attached to their aromatic rings may be active in scavenging the free radicals. The effectiveness of polyphenols in preventing tumor growth, angiogenesis, and metastasis also lies in their ability to counteract/repair DNA damage, induce tumor suppressor genes, and inhibit the MAPK, NF-kB, and JAK/STAT pathways that induce the expression of MMPs, TGF- β , and VEGF. Polyphenols, and their combination, would be effective in the prevention of cancer or as supplements in the treatment of cancer.