Oral administration of Polypodium leucotomos delays skin tumor development and increases epidermal p53 expression and the anti‐oxidant status of UV‐irradiated hairless mice

Abstract

Additional Supporting Information may be found in the online version of this article:Data S1. Methods. Table S1. Sequences of StealthTM siRNA. Table S2. Summary of antibodies and conditions used in immunohistochemistry. Figure S1. siRNA-silencing of genes individually or in combination in organotypic skin cultures reduced the expression of target genes effectively. Figure S2. Western blot analysis of 3D cultures showed a decrease of the accumulation of (pro)filaggrin, DSC1, DSG1 in SPINK5 kd cultures, but not in the double knockdowns. Abstract: Chronic exposure to ultraviolet radiation (UVR) induces skin tumors in hairless mice. Daily oral administration of a Polypodium leucotomos (PL) extract significantly delayed tumor development in PL-treated versus non-PL-treated mice. UVR and/or PL treatment modified several oxidative stress markers. In all irradiated mice, erythrocytic glutathione Stransferase (GST) activity and glutathione disulphide (GSSG) content increased and in all PL-treated mice GSSG content decreased, specially in non-irradiated animals, and total plasma anti-oxidant capacity (ORAC) increased. In dorsolateral nontumoral skin of all irradiated mice, glutathione reductase (GR) and glutathione peroxidase (GPx) activities increased and GSSG decreased in non-irradiated PL-treated animals. UVR induced a steep increase of p53 expression in epidermal cells. In nontumoral skin, this increase was significantly higher in PL-treated animals than in non-treated mice and can contribute in delaying tumor development, either by repairing the damaged DNA or by increasing apoptosis. These results reinforce the usefulness of PL as systemic photoprotective agent, especially in patients highly sensitive to UVR.

Thai herbal antipyretic 22 formula (APF22) inhibits UVA‐mediated melanogenesis through activation of Nrf2‐regulated antioxidant defense

“…CAT and GPx are important antioxidant enzymes that remove H 2 O 2 involved in triggering melanogenesis (Kasraee et al, ; Park, Sekhon, Yoon, Kim, & Min, ). GST is also a crucial detoxifying enzyme participating in the defense mechanisms against photodamaged skin and melanogenesis (Panich et al, ; Rodríguez‐Yanes, Cuevas, González, & Mallol, ).…”

Polypodium leucotomos: A Potential New Photoprotective Agent

“…Recently published data suggested the antioxidant effects of oral PLE led to significantly delayed tumor development (p = 0.023) in mice models, which could lead to further investigation into the agent's photoprotective nature [7]. The research team at the School of Medicine of Reus in Spain that conducted the study examined hairless mice irradiated with UV.…”

“…They followed several important markers to assess the role of oxidative stress to determine whether daily oral administration of PLE could delay or prevent tumor formation by increasing antioxidant defenses and epidermal p53 expression. Taking into account that immunosuppressive effects of UV radiation can have both cutaneous and systemic consequences, there were assessments of Langerhans cell activity, p53 expression, and Ki-67 expression to follow changes in epidermal proliferation [7]. There were several notable observations from the study.…”

“…These effects have been considered to contribute to slowing tumorigenesis, and proposed photoprotective effects, linked to the antioxidant properties of PLE. On the basis of the objective reduction in tumor development and the laboratory findings, it was the hypothesis of the authors that the photoprotective effect of oral PLE may benefit patients with cumulative UV exposure [7].…”

Melanomagenesis: multifaceted attacks on the genome

“…Further, products that drive eumelanin synthesis over pheomelanin synthesis could reduce amyloid exposure. Oral antioxidants, such as Lycopene and the Polypodium leucotomos fern extract , may also play a role. In addition, topical antioxidants may be beneficial .…”