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The characteristics of malignancy are cell growth and remodeling 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, 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-kB)/p65, and JAK/STAT (Signal Transduction and Activation of Transcription) that, 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, anthocyanin, 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. In addition, the effectiveness of polyphenols is improved in combination with nanobiomaterials such as chitosan, polymeric nanoparticles, nanoconjugates, liposomes, or a phage system.

The hallmarks of cancer include cell growth and metastasis, facilitated by angiogenesis and the remodeling of the extracellular matrix (ECM) by vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), transforming growth factor (TGF-β) and matrixmetalloproteinases (MMPs), which are the predominant factors. These factors are secreted by tumors or the stromal cells in the tumor niche. Oxidative stress and inflammation are the primary causes of the pro-angiogenic factors, including VEGF, MMPs, TGF-β, and IL-8 that collectively activate several signal transduction pathways such as MAP kinase and NF-kB to accentuate ECM remodeling, angiogenesis and cancer metastasis. Ascorbate (Vitamin C) is a major regulator of the ECM and regulates cancer biology. It inhibits the invasiveness of several cancers such as gastric, oral, pulmonary, fibrosarcoma and melanoma. We have reported ascorbate’s dose-dependent inverse effects on cancer cell growth and the expression MMPs and TGF-β. An extract from P. leucotomos (a fern) in combination with ascorbate simultaneously reduces cancer cell growth as well as the expression of MMP-1 and TGF-β. Further, ascorbate and P. leucotomos, independently and in combination, inhibit the expression of VEGF in a dose dependent manner. A combination of ascorbate and P. leucotomos would benefit as preventive measure; and well as a supplemental regimen for cancer patients.

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.

Skin aging is associated with the loss of the structural collagens and the elastin fiber components that form the extracellular matrix (ECM). It is associated with reduced transforming growth factor-β (TGF-β), angiogenesis and increased oxidative stress. Copper has been incorporated into cosmetics for anti-skin aging. This research investigated the mechanism for the anti-skin aging effect copper ions, from cuprous oxide powders. Dermal fibroblasts were exposed to copper and examined for expression (protein and/or promoter levels) of types I, III, V collagen, heat shock protein-47 (HSP-47), elastin, fibrillin-1, and fibrillin-2, TGF-β1, vascular endothelial growth factor (VEGF), and in addition for membrane damage and lipid peroxidation. The direct antioxidant activity of copper was also determined. The research indicates that copper's anti-skin aging and skin regeneration potential is through its stimulation of ECM proteins, TGF-β1, VEGF, and inhibition of oxidative stress effects at physiological concentrations; and supports its use in cosmetics.