Cited by 69Skin Protection and Agingmelanin and skin pigmentationNonmelanoma Skin Cancer Studies

Molecular photoprotection of human keratinocytes in vitro by the naturally occurring mycosporine-like amino acid palythine

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Lawrence, K.P., Gacesa, R., Long, P.F., Young, A.R.·2018·British Journal of Dermatology

Abstract

BACKGROUND: Solar ultraviolet radiation (UVR) induces molecular and genetic changes in the skin, which result in skin cancer, photoageing and photosensitivity disorders. The use of sunscreens is advocated to prevent such photodamage; however, most formulations contain organic and inorganic UVR filters that are nonbiodegradable and can damage fragile marine ecosystems. Mycosporine-like amino acids (MAAs) are natural UVR-absorbing compounds that have evolved in marine species for protection against chronic UVR exposure in shallow-water habitats. OBJECTIVES: To determine if palythine, a photostable model MAA, could offer protection against a range of UVR-induced damage biomarkers that are important in skin cancer and photoageing. METHODS: HaCaT human keratinocytes were used to assess the photoprotective potential of palythine using a number of end points including cell viability, DNA damage (nonspecific, cyclobutane pyrimidine dimers and oxidatively generated damage), gene expression changes (linked to inflammation, photoageing and oxidative stress) and oxidative stress. The antioxidant mechanism was investigated using chemical quenching and Nrf2 pathway activation assays. RESULTS: Palythine offered statistically significant protection (P < 0·005) against all end points tested even at extremely low concentrations (0·3% w/v). Additionally, palythine was found to be a potent antioxidant, reducing oxidatively generated stress, even when added after exposure. CONCLUSIONS: Palythine is an extremely effective multifunctional photoprotective molecule in vitro that has potential to be developed as a natural and biocompatible alternative to currently approved UVR filters.

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  • Cyanobacteria contain defense mechanisms, including production of UV-absorbing compounds such as mycosporine-like amino acids and enzymes such as superoxide dismutases, which help minimize the effects of oxidative stress.

    “Cyanobacteria contain a variety of defense mechanisms, including the production of UV-absorbing compounds such as mycosporine-like amino acids and enzymes such as superoxide dismutases, which help to minimize the effects of oxidative stress (Lawrence et al. 2018).”

    From Skin protection from solar ultraviolet radiation using natural compounds: a review (2024) · cites this paper as Lawrence et al. 2018

    The Background and discussion passages (page unavailable) describe MAAs as UV-absorbing compounds with photoprotective and antioxidant properties; the References list work on MAAs in cyanobacteria. The paper does not say that cyanobacteria produce superoxide dismutases as a defense against oxidative stress. Its only mention of superoxide dismutase is in a reference about human keratinocytes. (LLM, conf=0.83)

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  1. [1]Young AR, Chadwick CA, Harrison GI et al The similarity of action spectra for thymine dimers in human epidermis and erythema suggests that DNA is the chromophore for erythema. J Invest Dermatol 1998; 111: 982– 8. 9856805
  2. [3]Bickers DR, Athar M. Oxidative stress in the pathogenesis of skin disease. J Invest Dermatol 2006; 126: 2565– 75. 17108903
  3. [5]Rochette PJ, Lacoste S, Therrien JP et al Influence of cytosine methylation on ultraviolet‐induced cyclobutane pyrimidine dimer formation in genomic DNA. Mutat Res 2009; 665: 7– 13. 19427505
  4. [6]Kibitel J, Hejmadi V, Alas L et al UV‐DNA damage in mouse and human cells induces the expression of tumor necrosis factor alpha. Photochem Photobiol 1998; 67: 541– 6. 9644008
  5. [7]Nishigori C, Yarosh DB, Ullrich SE et al Evidence that DNA damage triggers interleukin 10 cytokine production in UV‐irradiated murine keratinocytes. Proc Natl Acad Sci U S A 1996; 93: 10354– 9. 8816804 PMC38388
  6. [8]Huang XX, Scolyer RA, Abubakar A et al Human 8‐oxoguanine‐DNA glycosylase‐1 is downregulated in human basal cell carcinoma. Mol Genet Metab 2012; 106: 127– 30. 22436579
  7. [9]Kutlubay Z, Sevim A, Engin B et al Photodermatoses, including phototoxic and photoallergic reactions (internal and external). Clin Dermatol 2014; 32: 73– 9. 24314379
  8. [10]Quan T, Qin Z, Xia W et al Matrix‐degrading metalloproteinases in photoaging. J Investig Dermatol Symp Proc 2009; 14: 20– 4. PMC2909639 19675548
  9. [11]Thompson SC, Jolley D, Marks R. Reduction of solar keratoses by regular sunscreen use. N Engl J Med 1993; 329: 1147– 51. 8377777
  10. [12]Naylor MF, Boyd A, Smith DW et al High sun protection factor sunscreens in the suppression of actinic neoplasia. Arch Dermatol 1995; 131: 170– 5. 7857113
  11. [13]Green AC, Williams GM. Point: sunscreen use is a safe and effective approach to skin cancer prevention. Cancer Epidemiol Biomarkers Prev 2007; 16: 1921– 2. 17932337
  12. [14]Iannacone MR, Hughes MC, Green AC. Effects of sunscreen on skin cancer and photoaging. Photodermatol Photoimmunol Photomed 2014; 30: 55– 61. 24417448
  13. [15]Deleo V. Sunscreen use in photodermatoses. Dermatol Clin 2006; 24: 27– 33. 16311165
  14. [16]Lenane P, Murphy GM. Sunscreens and the photodermatoses. J Dermatolog Treat 2001; 12: 53– 7. 12171690
  15. [17]Cardozo KH, Guaratini T, Barros MP et al Metabolites from algae with economical impact. Comp Biochem Physiol C Toxicol Pharmacol 2007; 146: 60– 78. 16901759
  16. [18]Tovar‐Sanchez A, Sanchez‐Quiles D, Basterretxea G et al Sunscreen products as emerging pollutants to coastal waters. PLoS One 2013; 8: e65451. 23755233 PMC3673939
  17. [19]Fent K, Zenker A, Rapp M. Widespread occurrence of estrogenic UV‐filters in aquatic ecosystems in Switzerland. Environ Pollut 2010; 158: 1817– 24. 20004505
  18. [20]Danovaro R, Bongiorni L, Corinaldesi C et al Sunscreens cause coral bleaching by promoting viral infections. Environ Health Perspect 2008; 116: 441– 7. 18414624 PMC2291018
  19. [21]Tibbetts J. Bleached, but not by the sun: sunscreen linked to coral damage. Environ Health Perspect 2008; 116: A173. PMC2291012 18414619
  20. [22]Weston AJ, Dunlap WC, Shick JM et al A profile of an endosymbiont‐enriched fraction of the coral Stylophora pistillata reveals proteins relevant to microbial‐host interactions. Mol Cell Proteomics 2012; 11: M111.015487. PMC3433924 22351649
  21. [23]Downs CA, Kramarsky‐Winter E, Fauth JE et al Toxicological effects of the sunscreen UV filter, benzophenone‐2, on planulae and in vitro cells of the coral, Stylophora pistillata. Ecotoxicology 2014; 23: 175– 91. 24352829
  22. [24]Chisvert A, Leon‐Gonzalez Z, Tarazona I et al An overview of the analytical methods for the determination of organic ultraviolet filters in biological fluids and tissues. Anal Chim Acta 2012; 752: 11– 29. 23101648
  23. [27]Kunz PY, Gries T, Fent K. The ultraviolet filter 3‐benzylidene camphor adversely affects reproduction in fathead minnow (Pimephales promelas). Toxicol Sci 2006; 93: 311– 21. 16870688
  24. [28]Weisbrod CJ, Kunz PY, Zenker AK et al Effects of the UV filter benzophenone‐2 on reproduction in fish. Toxicol Appl Pharmacol 2007; 225: 255– 66. 17889917
  25. [29]de Groot AC, Roberts DW. Contact and photocontact allergy to octocrylene: a review. Contact Dermatitis 2014; 70: 193– 204. 24628344
  26. [30]Karlsson I, Vanden Broecke K, Martensson J et al Clinical and experimental studies of octocrylene's allergenic potency. Contact Dermatitis 2011; 64: 343– 52. 21504434
  27. [31]Okuda‐Shimazaki J, Takaku S, Kanehira K et al Effects of titanium dioxide nanoparticle aggregate size on gene expression. Int J Mol Sci 2010; 11: 2383– 92. 20640159 PMC2904923
  28. [32]Becker K, Schroecksnadel S, Geisler S et al TiO(2) nanoparticles and bulk material stimulate human peripheral blood mononuclear cells. Food Chem Toxicol 2014; 65: 63– 9. 24361406 PMC3969306
  29. [33]Burnett ME, Wang SQ. Current sunscreen controversies: a critical review. Photodermatol Photoimmunol Photomed 2011; 27: 58– 67. 21392107
  30. [34]Bais AF, Lucas RM, Bornman JF et al Environmental effects of ozone depletion, UV radiation and interactions with climate change: UNEP Environmental Effects Assessment Panel, 2017. Photochem Photobiol Sci 2018; 17: 127– 79. 29404558 PMC6155474
  31. [35]Kim S, Seock Y‐K. Impacts of health and environmental consciousness on young female consumers' attitude towards and purchase of natural beauty products. Int J Consum Stud 2009; 33: 627– 38.
  32. [36]Garbutcheon‐Singh KB, Dixit S, Lee A et al Assessment of attitudes towards sun‐protective behaviour in Australians: a cross‐sectional study. Australas J Dermatol 2016; 57: 102– 7. 25823588
  33. [37]Kensler TW, Wakabayashi N, Biswal S. Cell survival responses to environmental stresses via the Keap1‐Nrf2‐ARE pathway. Annu Rev Pharmacol Toxicol 2007; 47: 89– 116. 16968214
  34. [39]Shick JM, Dunlap WC. Mycosporine‐like amino acids and related Gadusols: biosynthesis, accumulation, and UV‐protective functions in aquatic organisms. Annu Rev Physiol 2002; 64: 223– 62. 11826269
  35. [41]Gacesa R, Dunlap WC, Long PF. Bioinformatics analyses provide insight into distant homology of the Keap1‐Nrf2 pathway. Free Radic Biol Med 2015; 88: 373– 80. 26117326
  36. [44]Tsujino T, Yabe K, Sekikawa I et al Isolation and structure of a mycosporine from the red alga chondrus yendoi. Tetrahedron Lett 1978; 16: 1401– 2.
  37. [45]Repetto G, del Peso A, Zurita JL. Neutral red uptake assay for the estimation of cell viability/cytotoxicity. Nat Protoc 2008; 3: 1125– 31. 18600217
  38. [46]Karbaschi M, Macip S, Mistry V et al Rescue of cells from apoptosis increases DNA repair in UVB exposed cells: implications for the DNA damage response. Toxicol Res 2015; 4: 725– 38.
  39. [47]Azqueta A, Collins AR. The comet assay: a sensitive and quantitative method for analysis of DNA damage In: Encyclopedia of Analytical Chemistry (Meyers RA, ed.). New York: John Wiley & Sons, 2011.
  40. [48]Kalyanaraman B, Darley‐Usmar V, Davies KJ et al Measuring reactive oxygen and nitrogen species with fluorescent probes: challenges and limitations. Free Radic Biol Med 2012; 52: 1– 6. 22027063 PMC3911769
  41. [49]Krishna MC, Dewhirst MW, Friedman HS et al Hyperthermic sensitization by the radical initiator 2,2′‐azobis (2‐amidinopropane) dihydrochloride (AAPH). I. In vitro studies. Int J Hyperthermia 1994; 10: 271– 81. 8064185
  42. [50]Cao G, Alessio HM, Cutler RG. Oxygen‐radical absorbance capacity assay for antioxidants. Free Radic Biol Med 1993; 14: 303– 11. 8458588
  43. [51]Hancock R, Bertrand HC, Tsujita T et al Peptide inhibitors of the Keap1‐Nrf2 protein‐protein interaction. Free Radic Biol Med 2012; 52: 444– 51. 22107959
  44. [52]Zhuang C, Narayanapillai S, Zhang W et al Rapid identification of Keap1‐Nrf2 small‐molecule inhibitors through structure‐based virtual screening and hit‐based substructure search. J Med Chem 2014; 57: 1121– 6. 24417449
  45. [53]Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real‐time quantitative PCR and the 2(‐Delta Delta C(T)) method. Methods 2001; 25: 402– 8. 11846609
  46. [54]Tewari A. The cellular and molecular effects of UVA1 on human skin in vivo: impact on human health. PhD thesis, St. John's Institute of Dermatology, King's College, London, 2015.
  47. [55]Maier H, Schauberger G, Brunnhofer K et al Change of ultraviolet absorbance of sunscreens by exposure to solar‐simulated radiation. J Invest Dermatol 2001; 117: 256– 62. 11511302
  48. [56]Conde FR, Churio MS, Previtali CM. Experimental study of the excited‐state properties and photostability of the mycosporine‐like amino acid palythine in aqueous solution. Photochem Photobiol Sci 2007; 6: 669– 74. 17549269
  49. [57]Whitehead K, Hedges JI. Photodegradation and photosensitization of mycosporine‐like amino acids. J Photochem Photobiol, B 2005; 80: 115– 21. 15893470
  50. [58]Marionnet C, Pierrard C, Golebiewski C et al Diversity of biological effects induced by longwave UVA rays (UVA1) in reconstructed skin. PLoS One 2014; 9: e105263. 25140898 PMC4139344
  51. [59]Diffey B. Solar spectral irradiance and summary outputs using excel. Photochem Photobiol 2015; 91: 553– 7. 25644778
  52. [60]Harrison GI, Young AR. Ultraviolet radiation‐induced erythema in human skin. Methods 2002; 28: 14– 19. 12231183
  53. [61]Sasaki H, Akamatsu H, Horio T. Protective role of copper, zinc superoxide dismutase against UVB‐induced injury of the human keratinocyte cell line HaCaT. J Invest Dermatol 2000; 114: 502– 7. 10692109
  54. [62]Sporl F, Schellenberg K, Blatt T et al A circadian clock in HaCaT keratinocytes. J Invest Dermatol 2011; 131: 338– 48. 20962856
  55. [64]Afaq F, Syed DN, Malik A et al Delphinidin, an anthocyanidin in pigmented fruits and vegetables, protects human HaCaT keratinocytes and mouse skin against UVB‐mediated oxidative stress and apoptosis. J Invest Dermatol 2007; 127: 222– 32. 16902416
  56. [65]Torres A, Hochberg M, Pergament I et al A new UV‐B absorbing mycosporine with photo protective activity from the lichenized ascomycete Collema cristatum. Eur J Biochem 2004; 271: 780– 4. 14764094
  57. [66]Ryu J, Park SJ, Kim IH et al Protective effect of porphyra‐334 on UVA‐induced photoaging in human skin fibroblasts. Int J Mol Med 2014; 34: 796– 803. 24946848 PMC4121349
  58. [67]Nazifi E, Wada N, Yamaba M et al Glycosylated porphyra‐334 and palythine‐threonine from the terrestrial cyanobacterium Nostoc commune. Mar Drugs 2013; 11: 3124– 54. 24065157 PMC3801118
  59. [69]Ahmad I, Sheraz MA, Ahmed S et al Photostability and interaction of ascorbic acid in cream formulations. AAPS PharmSciTech 2011; 12: 917– 23. 21735345 PMC3167265
  60. [70]Neunert G, Szwengiel A, Walejko P et al Photostability of alpha‐tocopherol ester derivatives in solutions and liposomes. Spectroscopic and LC‐MS studies. J Photochem Photobiol, B 2016; 160: 121– 7. 27107331
  61. [71]Herzog B, Osterwalder U. Simulation of sunscreen performance. Pure Appl Chem 2015; 87: 937– 51.
  62. [72]Takano S, Uemura D, Hirata Y. Isolation and structure of a new amino acid, palythine, from the zoanthid Palythoa tuberculosa. Tetrahedron Lett 1978; 26: 2299– 300.
  63. [73]Shaath NA. Ultraviolet filters. Photochem Photobiol Sci 2010; 9: 464– 9. 20354639

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Authors
Lawrence, K. P., Gacesa, R., Long, P. F., & Young, A. R.
Affiliations
  • King's College London (GB)
  • Institute of Pharmaceutical Science; Faculty of Life Sciences and Medicine; King's College London; London U.K.
Corresponding author
Young, A.R.
Venue
British Journal of Dermatology
Published
2018-03-25
Volume
178
Issue
6
Pages
1353-1363
ISSN
0007-0963 (ISSN-L)
OpenAlex
W2769031448
Cited by
69
References
10
Citations by year
2026: 6 · 2025: 6 · 2024: 4 · 2023: 14 · 2022: 9 · 2021: 9 · 2020: 8 · 2019: 8 · 2018: 5
FWCI
6.54
Type
journal article
Language
en
Open access
Locations
  • British Journal of Dermatology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research Portal (King's College London) (submittedVersion, cc-by)
Funders
  • BASF
  • National Institute for Health Research
Topics
  • Health Sciences › Medicine › Dermatology › Skin Protection and Aging
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
  • Health Sciences › Medicine › Epidemiology › Nonmelanoma Skin Cancer Studies
Keywords
palythine, mycosporine-like amino acids, photoprotection, ultraviolet radiation, keratinocytes, HaCaT keratinocytes, DNA damage, cyclobutane pyrimidine dimers, oxidative stress, antioxidant activity, Nrf2 signaling, photoaging, skin cancer, sunscreen
MeSH terms
Antioxidants, Cell Survival, Cells, Cultured, Cyclohexanols, DNA Damage, Glycine, Humans, Radiation Dosage, Skin Neoplasms, Sunlight, Sunscreening Agents, Ultraviolet Rays, Biomarkers, Skin Aging, Keratinocytes, Gene Expression, Cell Death, Oxidative Stress, In Vitro Techniques

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