Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
권호 표지
DOI QR코드

DOI QR Code

Extracellular Vesicles from Korean Codium fragile and Sargassum fusiforme Negatively Regulate Melanin Synthesis

  • Jang, Bohee (Department of Life Sciences, The Research Center for Cellular Homeostasis, Ewha Womans University) ;
  • Chung, Heesung (Department of Life Sciences, The Research Center for Cellular Homeostasis, Ewha Womans University) ;
  • Jung, Hyejung (Department of Life Sciences, The Research Center for Cellular Homeostasis, Ewha Womans University) ;
  • Song, Hyun-Kuk (Department of Life Sciences, The Research Center for Cellular Homeostasis, Ewha Womans University) ;
  • Park, Eunhye (Department of Life Sciences, The Research Center for Cellular Homeostasis, Ewha Womans University) ;
  • Choi, Hack Sun (Subtropical/Tropical Organism Gene Bank, Jeju National University) ;
  • Jung, Kyuhyun (ExoMed, Inc.) ;
  • Choe, Han (Department of Physiology, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Yang, Sanghwa (ExoMed, Inc.) ;
  • Oh, Eok-Soo (Department of Life Sciences, The Research Center for Cellular Homeostasis, Ewha Womans University)
  • Received : 2020.08.07
  • Accepted : 2021.08.17
  • Published : 2021.10.31
Download PDF
⟨ Previous Next ⟩

Abstract

Although various marine ingredients have been exploited for the development of cosmetic products, no previous study has examined the potential of seaweed extracellular vesicles (EV) in such applications. Our results revealed that EV from Codium fragile and Sargassum fusiforme effectively decreased α-MSH-mediated melanin synthesis in MNT-1 human melanoma cells, associated with downregulation of MITF (microphthalmia-associated transcription factor), tyrosinase and TRP1 (tyrosinase-related proteins 1). The most effective inhibitory concentrations of EV were 250 ㎍/ml for S. fusiforme and 25 ㎍/ml for C. fragile, without affecting the viability of MNT-1 cells. Both EV reduced melanin synthesis in the epidermal basal layer of a three-dimensional model of human epidermis. Moreover, the application of the prototype cream containing C. fragile EV (final 5 ㎍/ml) yielded 1.31% improvement in skin brightness in a clinical trial. Together, these results suggest that EV from C. fragile and S. fusiforme reduce melanin synthesis and may be potential therapeutic and/or supplementary whitening agents.

Keywords

Acknowledgement

This work was supported by the project titled 'development of skin functional material using seaweed extracellular vesicle', funded by the Ministry of Oceans and Fisheries, Korea (20190067). We thank the electron microscopy core facility at the ConveRgence mEDIcine research cenTer (CREDIT), Asan Medical Center, Seoul, Korea, for support and instrumentation. This electron microscopy was performed by the core facility at the ConveRgence mEDIcine research cenTer (CREDIT), Asan Medical Center, Seoul, Korea. Written informed consent was obtained from the participants for publication of this article and accompanying images.

References

  1. Antimisiaris, S.G., Mourtas, S., and Marazioti, A. (2018). A exosomes and exosome-inspired vesicles for targeted drug delivery. Pharmaceutics 10, 218. https://doi.org/10.3390/pharmaceutics10040218
  2. Archambault, M., Yaar, M., and Gilchrest, B.A. (1995). Keratinocytes and fibroblasts in a human skin equivalent model enhance melanocyte survival and melanin synthesis after ultraviolet irradiation. J. Invest. Dermatol. 104, 859-867. https://doi.org/10.1111/1523-1747.ep12607034
  3. Arulmozhi, V., Pandian, K., and Mirunalini, S. (2013). Ellagic acid encapsulated chitosan nanoparticles for drug delivery system in human oral cancer cell line (KB). Colloids Surf. B Biointerfaces 110, 313-320. https://doi.org/10.1016/j.colsurfb.2013.03.039
  4. Azmi, A.S., Bao, B., and Sarkar, F.H. (2013). Exosomes in cancer development, metastasis, and drug resistance: a comprehensive review. Cancer Metastasis Rev. 32, 623-642. https://doi.org/10.1007/s10555-013-9441-9
  5. Baroni, A., Buommino, E., De Gregorio, V., Ruocco, E., Ruocco, V., and Wolf, R. (2012). Structure and function of the epidermis related to barrier properties. Clin. Dermatol. 30, 257-262. https://doi.org/10.1016/j.clindermatol.2011.08.007
  6. Bastonini, E., Kovacs, D., and Picardo, M. (2016). Skin pigmentation and pigmentary disorders: focus on epidermal/dermal cross-talk. Ann. Dermatol. 28, 279-289. https://doi.org/10.5021/ad.2016.28.3.279
  7. Brenner, M. and Hearing, V.J. (2008). The protective role of melanin against UV damage in human skin. Photochem. Photobiol. 84, 539-549. https://doi.org/10.1111/j.1751-1097.2007.00226.x
  8. Cha, S.H., Ko, S.C., Kim, D., and Jeon, Y.J. (2011). Screening of marine algae for potential tyrosinase inhibitor: those inhibitors reduced tyrosinase activity and melanin synthesis in zebra fish. J. Dermatol. 38, 354-363. https://doi.org/10.1111/j.1346-8138.2010.00983.x
  9. Chan, Y.Y., Kim, K.H., and Cheah, S.H. (2011). Inhibitory effects of Sargassum polycystum on tyrosinase activity and melanin formation in B16F10 murine melanoma cells. J. Ethnopharmacol. 137, 1183-1188. https://doi.org/10.1016/j.jep.2011.07.050
  10. Cunha, L. and Grenha, A. (2016). Sulfated seaweed polysaccharides as multifunctional materials in drug delivery applications. Mar. Drugs 14, 42. https://doi.org/10.3390/md14030042
  11. Dores, R.M. and Baron, A.J. (2011). Evolution of POMC: origin, phylogeny, posttranslational processing, and the melanocortins. Ann. N. Y. Acad. Sci. 1220, 34-48. https://doi.org/10.1111/j.1749-6632.2010.05928.x
  12. Draelos, Z.D. (2007). Skin lightening preparations and the hydroquinone controversy. Dermatol. Ther. 20, 308-313. https://doi.org/10.1111/j.1529-8019.2007.00144.x
  13. Ferreira, J., Ramos, A.A., Almeida, T., Azqueta, A., and Rocha, E. (2018). Drug resistance in glioblastoma and cytotoxicity of seaweed compounds, alone and in combination with anticancer drugs: a mini review. Phytomedicine 48, 84-93. https://doi.org/10.1016/j.phymed.2018.04.062
  14. Fujimoto, N., Onodera, H., Mitsumori, K., Tamura, T., Maruyama, S., and Ito, A. (1999). Changes in thyroid function during development of thyroid hyperplasia induced by kojic acid in F344 rats. Carcinogenesis 20, 1567-1571. https://doi.org/10.1093/carcin/20.8.1567
  15. Gomari, H., Moghadam, M.F., and Soleimani, M. (2018). Targeted cancer therapy using engineered extracellular vesicle as a natural drug delivery vehicle. Onco Targets Ther. 11, 5753-5762. https://doi.org/10.2147/OTT.S173110
  16. Hearing, V.J. (2011). Determination of melanin synthetic pathways. J. Invest. Dermatol. 131(E1), E8-E11. https://doi.org/10.1038/skinbio.2011.4
  17. Hedley, S.J., Gawkrodger, D.J., Weetman, A.P., and Macneil, S. (1998). alpha-MSH and melanogenesis in normal human adult melanocytes. Pigment Cell Res. 11, 45-56. https://doi.org/10.1111/j.1600-0749.1998.tb00710.x
  18. Hu, S., Li, Z., Cores, J., Huang, K., Su, T., Dinh, P.U., and Cheng, K. (2019). Needle-free injection of exosomes derived from human dermal fibroblast spheroids ameliorates skin photoaging. ACS Nano 13, 11273-11282. https://doi.org/10.1021/acsnano.9b04384
  19. Jin, Y., Kim, J.H., Hong, H.D., Kwon, J., Lee, E.J., Jang, M., Lee, S.Y., Han, A.R., Nam, T.G., Hong, S.K., et al. (2018). Ginsenosides Rg5 and Rk1, the skin-whitening agents in black ginseng. J. Funct. Foods 45, 67-74. https://doi.org/10.1016/j.jff.2018.03.036
  20. Jung, H., Chung, H., Chang, S.E., Choi, S., Han, I.O., Kang, D.H., and Oh, E.S. (2014). Syndecan-2 regulates melanin synthesis via protein kinase C betaII-mediated tyrosinase activation. Pigment Cell Melanoma Res. 27, 387-397. https://doi.org/10.1111/pcmr.12223
  21. Jung, H., Chung, H., Chang, S.E., Kang, D.H., and Oh, E.S. (2016). FK506 regulates pigmentation by maturing the melanosome and facilitating their transfer to keratinocytes. Pigment Cell Melanoma Res. 29, 199-209 https://doi.org/10.1111/pcmr.12443
  22. Kahan, V., Andersen, M.L., Tomimori, J., and Tufik, S. (2009). Stress, immunity and skin collagen integrity: evidence from animal models and clinical conditions. Brain Behav. Immun. 23, 1089-1095. https://doi.org/10.1016/j.bbi.2009.06.002
  23. Kang, H.S., Kim, H.R., Byun, D.S., Son, B.W., Nam, T.J., and Choi, J.S. (2004). Tyrosinase inhibitors isolated from the edible brown alga Ecklonia stolonifera. Arch. Pharm. Res. 27, 1226-1232. https://doi.org/10.1007/BF02975886
  24. Kim, N.H., Choi, S.H., Kim, C.H., Lee, C.H., Lee, T.R., and Lee, A.Y. (2014). Reduced MiR-675 in exosome in H19 RNA-related melanogenesis via MITF as a direct target. J. Invest. Dermatol. 134, 1075-1082. https://doi.org/10.1038/jid.2013.478
  25. Ko, R.K., Kang, M.C., Kim, S.S., Oh, T.H., Kim, G.O., Hyun, C.G., Hyun, J.W., and Lee, N.H. (2013). Anti-melanogenesis constituents from the seaweed Dictyota coriacea. Nat. Prod. Commun. 8, 427-428.
  26. Kwon, C., Lee, J.H., and Yun, H.S. (2020). SNAREs in plant biotic and abiotic stress responses. Mol. Cells 43, 501-508. https://doi.org/10.14348/molcells.2020.0007
  27. Lane, R.E., Korbie, D., Anderson, W., Vaidyanathan, R., and Trau, M. (2015). Analysis of exosome purification methods using a model liposome system and tunable-resistive pulse sensing. Sci. Rep. 5, 7639. https://doi.org/10.1038/srep07639
  28. Naval, P. and Chandra, T.S. (2019). Characterization of membrane vesicles secreted by seaweed associated bacterium Alteromonas macleodii KS62. Biochem. Biophys. Res. Commun. 514, 422-427. https://doi.org/10.1016/j.bbrc.2019.04.148
  29. Nicolaidou, E. and Katsambas, A.D. (2014). Pigmentation disorders: hyperpigmentation and hypopigmentation. Clin. Dermatol. 32, 66-72. https://doi.org/10.1016/j.clindermatol.2013.05.026
  30. Oh, M., Lee, J., Kim, Y., Rhee, W., and Park, J. (2018). Exosomes derived from human induced pluripotent stem cells ameliorate the aging of skin fibroblasts. Int. J. Mol. Sci. 19, 1715 https://doi.org/10.3390/ijms19061715
  31. Park, J., Jung, H., Kim, K., Lim, K.M., Kim, J.Y., Jho, E.H., and Oh, E.S. (2018). D-tyrosine negatively regulates melanin synthesis by competitively inhibiting tyrosinase activity. Pigment Cell Melanoma Res. 31, 374-383. https://doi.org/10.1111/pcmr.12668
  32. Parvez, S., Kang, M., Chung, H.S., Cho, C., Hong, M.C., Shin, M.K., and Bae, H. (2006). Survey and mechanism of skin depigmenting and lightening agents. Phytother. Res. 20, 921-934. https://doi.org/10.1002/ptr.1954
  33. Pillaiyar, T., Manickam, M., and Namasivayam, V. (2017). Skin whitening agents: medicinal chemistry perspective of tyrosinase inhibitors. J. Enzyme Inhib. Med. Chem. 32, 403-425. https://doi.org/10.1080/14756366.2016.1256882
  34. Saraswati, Giriwono, P.E., Iskandriati, D., Tan, C.P., and Andarwulan, N. (2019). Sargassum seaweed as a source of anti-inflammatory substances and the potential insight of the tropical species: a review. Mar. Drugs 17, 590. https://doi.org/10.3390/md17100590
  35. Shilabin, A.G. and Hamann, M.T. (2011). In vitro and in vivo evaluation of select kahalalide F analogs with antitumor and antifungal activities. Bioorg. Med. Chem. 19, 6628-6632 https://doi.org/10.1016/j.bmc.2011.06.050
  36. Solano, F., Briganti, S., Picardo, M., and Ghanem, G. (2006). Hypopigmenting agents: an updated review on biological, chemical and clinical aspects. Pigment Cell Res. 19, 550-571. https://doi.org/10.1111/j.1600-0749.2006.00334.x
  37. Spinola, V., Mendes, B., Camara, J.S., and Castilho, P.C. (2013). Effect of time and temperature on vitamin C stability in horticultural extracts. UHPLC-PDA vs. iodometric titration as analytical methods. Lebensm. Wiss. Technol. 50, 489-495. https://doi.org/10.1016/j.lwt.2012.08.020
  38. Valadi, H., Ekstrom, K., Bossios, A., Sjostrand, M., Lee, J.J., and Lotvall, J.O. (2007). Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat. Cell Biol. 9, 654-659. https://doi.org/10.1038/ncb1596
  39. van den Boorn, J.G., Picavet, D.I., van Swieten, P.F., van Veen, H.A., Konijnenberg, D., van Veelen, P.A., van Capel, T., de Jong, E.C., Reits, E.A., Drijfhout, J.W., et al. (2011). Skin-depigmenting agent monobenzone induces potent T-cell autoimmunity toward pigmented cells by tyrosinase haptenation and melanosome autophagy. J. Invest. Dermatol. 131, 1240-1251. https://doi.org/10.1038/jid.2011.16
  40. Venkatesan, J., Anil, S., Kim, S.K., and Shim, M. (2016). Seaweed polysaccharide-based nanoparticles: preparation, and applications for drug delivery. Polymers (Basel) 8, 30. https://doi.org/10.3390/polym8020030
  41. Yoon, N.Y., Eom, T.K., Kim, M.M., and Kim, S.K. (2009). Inhibitory effect of phlorotannins isolated from Ecklonia cava on mushroom tyrosinase activity and melanin formation in mouse B16F10 melanoma cells. J. Agric. Food Chem. 57, 4124-4129. https://doi.org/10.1021/jf900006f
  42. Zhou, H., Kepa, J.K., Siegel, D., Miura, S., Hiraki, Y., and Ross, D. (2009). Benzene metabolite hydroquinone up-regulates chondromodulin-I and inhibits tube formation in human bone marrow endothelial cells. Mol. Pharmacol. 76, 579-587. https://doi.org/10.1124/mol.109.057323