An Experimental Double-Blind Irradiation Study of a Novel Topical Product (TPF 50) Compared to Other Topical Products With DNA Repair Enzymes, Antioxidants, and Growth Factors With Sunscreens: Implications for Preventing Skin Aging and Cancer
March 2014 | Volume 13 | Issue 3 | Original Article | 309 | Copyright © March 2014
Enzo Emanuele MD PhD,a James M. Spencer MD MS,b and Martin Braun MDc
aLiving Research sas, Robbio (PV), Italy
bProfessor of Clinical Dermatology, Mt Sinai School of Medicine, New York, NY
The exposure to ultraviolet radiation (UVR) is a major risk factor for skin aging and the development of non-melanoma skin cancer (NMSC). Although traditional sunscreens remain the mainstay for the prevention of UVR-induced skin damage, they cannot ensure a complete protection against the whole spectrum of molecular lesions associated with UVR exposure. The formation of helix-distorting photoproducts such as cyclobutane pyrimidine dimers (CPD), as well as oxidative damage to DNA bases, including the formation of 8-oxo-7,8-dihydro-2â€™-deoxyguanosine (8OHdG) are among the key DNA lesions associated with photoaging and tumorigenesis. Besides DNA lesions, UVR-induced formation of free radicals can result in protein carbonylation (PC), a major form of irreversible protein damage that inactivates their biological function. This study compares a complex novel topical product (TPF50) consisting of three actives, ie, 1) traditional physical sunscreens (SPF 50), 2) a liposome-encapsulated DNA repair enzymes complex (photolyase, endonuclease, and 8-oxoguanine glycosylase [OGG1]), and 3) a potent antioxidant complex (carnosine, arazine, ergothionine) to existing products. Specifically, we assessed the ability of TFP50 vs those of DNA repair and antioxidant and growth factor topical products used with SPF 50 sunscreens in preventing CPD, 8OHdG, and PC formation in human skin biopsies after experimental irradiations. In head-to-head comparison studies, TPF50 showed the best efficacy in reducing all of the three molecular markers. The results indicated that the three TPF50 components had a synergistic effect in reducing CPD and PC, but not 8OHdG. Taken together, our results indicate that TPF50 improves the genomic and proteomic integrity of skin cells after repeated exposure to UVR, ultimately reducing the risk of skin aging and NMSC.
J Drugs Dermatol.
The exposure of human skin to solar ultraviolet radiation (UVR) results in the formation of DNA and protein photolesions that can give rise to photoaging and non-melanoma skin cancers (NMSC).1-3 DNA has been traditionally considered as the main target of UVR, and mutagenesis by direct and indirect DNA damage currently represents the principal paradigm of UVR-associated skin aging and carcinogenesis.4 In light of the paramount role played by DNA alterations in skin aging and cancer, the topical application of DNA repair enzymes has been proposed to enhance repair synthesis as early as 1991 thanks to the pioneering work of Daniel Yarosh.5,6 Several studies have subsequently demonstrated that different xenogenic DNA repair enzymes (photolyase, endonuclease, and 8-oxoguanine glycosylase [OGG1]) are useful for reversing UVR-induced DNA damage in human skin when applied topically in liposomal form.7-11 In this regard, photolyase plus sunscreens has been shown to be superior to sunscreens alone in reducing the formation of cyclobutane pyrimidine dimers (CPD) in irradiated human skin.9
The beneficial effect of topical DNA repair enzymes on CPD and p53 expression has been subsequently confirmed immunohistochemically in an 8-week, open-label prospective.8 In another irradiation study, the application of a sunscreen plus photolyase 30 minutes before irradiation and an endonuclease preparation immediately after irradiation completely abrogated telomere shortening and c-FOS gene hyperexpression induced by UVR.7 In a clinical study, DeBoyes et al12 have shown that topical application of a DNA repair liposome lotion over 48 weeks effectively reduced the number of actinic keratoses in normal individuals with moderate-to-severe photodamaged skin. Similar to DNA repair enzymes, topically