Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Fucoxanthin Protects Cultured Human Keratinocytes against Oxidative Stress by Blocking Free Radicals and Inhibiting Apoptosis

  • Zheng, Jian (School of Medicine and Institute for Nuclear Science and Technology, Jeju National University) ;
  • Piao, Mei Jing (School of Medicine and Institute for Nuclear Science and Technology, Jeju National University) ;
  • Keum, Young Sam (Department of Biochemistry, College of Pharmacy, Dongguk University) ;
  • Kim, Hye Sun (Cancer Research Institute, Seoul National University College of Medicine) ;
  • Hyun, Jin Won (School of Medicine and Institute for Nuclear Science and Technology, Jeju National University)
  • Received : 2013.04.16
  • Accepted : 2013.05.08
  • Published : 2013.07.31
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Abstract

Fucoxanthin is an important carotenoid derived from edible brown seaweeds and is used in indigenous herbal medicines. The aim of the present study was to examine the cytoprotective effects of fucoxanthin against hydrogen peroxide-induced cell damage. Fucoxanthin decreased the level of intracellular reactive oxygen species, as assessed by fluorescence spectrometry performed after staining cultured human HaCaT keratinocytes with 2',7'-dichlorodihydrofluorescein diacetate. In addition, electron spin resonance spectrometry showed that fucoxanthin scavenged hydroxyl radical generated by the Fenton reaction in a cell-free system. Fucoxanthin also inhibited comet tail formation and phospho-histone H2A.X expression, suggesting that it prevents hydrogen peroxide-induced cellular DNA damage. Furthermore, the compound reduced the number of apoptotic bodies stained with Hoechst 33342, indicating that it protected keratinocytes against hydrogen peroxide-induced apoptotic cell death. Finally, fucoxanthin prevented the loss of mitochondrial membrane potential. These protective actions were accompanied by the down-regulation of apoptosis-promoting mediators (i.e., B-cell lymphoma-2-associated ${\times}$ protein, caspase-9, and caspase-3) and the up-regulation of an apoptosis inhibitor (B-cell lymphoma-2). Taken together, the results of this study suggest that fucoxanthin defends keratinocytes against oxidative damage by scavenging ROS and inhibiting apoptosis.

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References

  1. Arranz, N., Haza, A. I., Garcia, A., Delgado, E., Rafter, J. and Morales, P. (2007) Effects of organosulfurs, isothiocyanates and vitamin C towards hydrogen peroxide-induced oxidative DNA damage (strand breaks and oxidized purines/pyrimidines) in human hepatoma cells. Chem. Biol. Interact. 169, 63-71. https://doi.org/10.1016/j.cbi.2007.05.006
  2. Beppu, F., Niwano, Y., Sato, E., Kohno, M., Tsukui, T., Hosokawa, M. and Miyashita, K. (2009a) In vitro and in vivo evaluation of mutagenicity of fucoxanthin (FX) and its metabolite fucoxanthinol (FXOH). J. Toxicol. Sci. 34, 693-698. https://doi.org/10.2131/jts.34.693
  3. Beppu, F., Niwano, Y., Tsukui, T., Hosokawa, M. and Miyashita, K. (2009b) Single and repeated oral dose toxicity study of fucoxanthin (FX), a marine carotenoid, in mice. J. Toxicol. Sci. 34, 510-510.
  4. Bottai, G., Mancina, R., Muratori, M., Di Gennaro, P. and Lotti, T. (2012) $17\beta$-estradiol protects human skin fi broblasts and keratinocytes against oxidative damage. J. Eur. Acad. Dermatol. Venereol. doi: 10.1111/j.1468-3083. [Epub ahead of print]
  5. Cadenas, E. and Davies, K. J. (2000) Mitochondrial free radical generation, oxidative stress, and aging. Free Radic. Biol. Med. 29, 222-230. https://doi.org/10.1016/S0891-5849(00)00317-8
  6. Carmichael, J., DeGraff, W. G., Gazdar, A. F., Minna, J. D. and Mitchell, J. B. (1987) Evaluation of a tetrazolium-based semiautomated colorimetric assay: assessment of chemosensitivity testing. Cancer Res. 47, 936-942.
  7. Chakravarti, B. and Chakravarti, D. N. (2007) Oxidative modifi cation of proteins: Age-related changes. Gerontology 53, 128-139. https://doi.org/10.1159/000097865
  8. Cory, S., Huang, D. C. and Adams, J. M. (2003) The Bcl-2 family: roles in cell survival and oncogenesis. Oncogene 22, 8590-8607. https://doi.org/10.1038/sj.onc.1207102
  9. Das, S. K., Ren, R., Hashimoto, T. and Kanazawa, K. (2010) Fucoxanthin induces apoptosis in osteoclast-like cells differentiated from RAW264. 7 cells. J. Agric. Food Chem. 58, 6090-6095. https://doi.org/10.1021/jf100303k
  10. Deavall, D. G., Martin, E. A., Horner, J. M. and Roberts, R. (2012) Druginduced oxidative stress and toxicity. J. Toxicol. 2012, 645460.
  11. Devasagayam, T., Tilak, J., Boloor, K., Sane, K., Ghaskadbi, S. and Lele, R. (2004) Free radicals and antioxidants in human health: current status and future prospects. J. Assoc. Physicians India 52, 794-804.
  12. Ditch, S. and Paull, T. T. (2012) The ATM protein kinase and cellular redox signaling: beyond the DNA damage response. Trends Biochem. Sci. 37, 15-22. https://doi.org/10.1016/j.tibs.2011.10.002
  13. D'Orazio, N., Gemello, E., Gammone, M. A., de Girolamo, M., Ficoneri, C. and Riccioni, G. (2012) Fucoxantin: A treasure from the sea. Mar. Drugs 10, 604-616. https://doi.org/10.3390/md10030604
  14. D'souza, D., Subhas, B. G., Shetty, S. R. and Balan, P. (2012) Estimation of serum malondialdehyde in potentially malignant disorders and post-antioxidant treated patients: A biochemical study. Contemp. Clin. Dent. 3, 448-451. https://doi.org/10.4103/0976-237X.107438
  15. Emerit, I. (1992) Free radicals and aging of the skin. EXS 62, 328-341.
  16. Frenkel, K. (1992) Carcinogen-mediated oxidant formation and oxidative DNA damage. Pharmacol. Ther. 53, 127-166. https://doi.org/10.1016/0163-7258(92)90047-4
  17. Fuchs, J., Hufl ejt, M. E., Rothfuss, L. M., Wilson, D. S., Carcamo, G. and Packer, L. (1989) Impairment of enzymic and nonenzymic antioxidants in skin by UVB irradiation. J. Invest. Dermatol. 93, 769-773. https://doi.org/10.1111/1523-1747.ep12284412
  18. Green, D. R. and Reed, J. C. (1998) Mitochondria and apoptosis. Science 281, 1309-1312. https://doi.org/10.1126/science.281.5381.1309
  19. Heo, S. J. and Jeon, Y. J. (2009) Protective effect of fucoxanthin isolated from Sargassum siliquastrum on UV-B induced cell damage. J. Photochem. Photobiol. B 95, 101-107. https://doi.org/10.1016/j.jphotobiol.2008.11.011
  20. Heo, S. J., Ko, S. C., Kang, S. M., Kang, H. S., Kim, J. P., Kim, S. H., Lee, K.W., Cho, M.G. and Jeon, Y. J. (2008) Cytoprotective effect of fucoxanthin isolated from brown algae Sargassum siliquastrum against $H_{2}O_{2}$-induced cell damage. Eur. Food Res. Technol. 228, 145-151. https://doi.org/10.1007/s00217-008-0918-7
  21. Hu, T., Liu, D., Chen, Y., Wu, J. and Wang, S. (2010) Antioxidant activity of sulfated polysaccharide fractions extracted from Undaria pinnitafi da in vitro. Int. J. Biol. Macromol. 46, 193-198. https://doi.org/10.1016/j.ijbiomac.2009.12.004
  22. Jeong, S. Y. and Seol, D. W. (2008) The role of mitochondria in apoptosis. BMB Rep. 41, 11-22. https://doi.org/10.5483/BMBRep.2008.41.1.011
  23. Khan, M. N., Cho, J. Y., Lee, M. C., Kang, J. Y., Park, N. G., Fujii, H. and Hong, Y. K. (2007) Isolation of two anti-infl ammatory and one pro-infl ammatory polyunsaturated fatty acids from the brown seaweed Undaria pinnatifi da. J. Agric. Food Chem. 55, 6984-6988. https://doi.org/10.1021/jf071791s
  24. Klaunig, J. E., Kamendulis, L. M. and Hocevar, B. A. (2010) Oxidative stress and oxidative damage in carcinogenesis. Toxicol. Pathol. 38, 96-109. https://doi.org/10.1177/0192623309356453
  25. Li, L., Abe, Y., Kanagawa, K., Usui, N., Imai, K., Mashino, T., Mochizuki, M. and Miyata, N. (2004) Distinguishing the 5, 5-dimethyl-1-pyrroline N-oxide (DMPO)-OH radical quenching effect from the hydroxyl radical scavenging effect in the ESR spin-trapping method. Anal. Chim. Acta 512, 121-124. https://doi.org/10.1016/j.aca.2004.02.020
  26. Li, R., Yan, G., Li, Q., Sun, H., Hu, Y., Sun, J. and Xu, B. (2012) MicroRNA-145 protects cardiomyocytes against hydrogen peroxide ($H_{2}O_{2}$)-induced apoptosis through targeting the mitochondria apoptotic pathway. PLoS One 7, e44907. https://doi.org/10.1371/journal.pone.0044907
  27. Licandro, G., Khor, H. L., Beretta, O., Lai, J., Derks, H., Laudisi, F., Conforti-Andreoni, C., Qian, H. L., Teng, G. G., Ricciardi-Castaqnoli, P. and Mortellaro, A. (2013) The NLRP3 infl ammasome affects DNA damage responses after oxidative and genotoxic stress in dendritic cells. Eur. J. Immunol. doi: 10.1002/eji. [Epub ahead of print]
  28. Liu, C. L., Chiu, Y. T. and Hu, M. L. (2011) Fucoxanthin enhances HO-1 and NQO1 expression in murine hepatic BNL CL. 2 cells through activation of the Nrf2/ARE system partially by its pro-oxidant activity. J. Agric. Food Chem. 59, 11344-11351. https://doi.org/10.1021/jf2029785
  29. Loeb, L. A., Wallace, D. C., and Martin, G. M. (2005) The mitochondrial theory of aging and its relationship to reactive oxygen species damage and somatic mtDNA mutations. Proc. Natl. Acad. Sci. U.S.A. 102, 18769-18770. https://doi.org/10.1073/pnas.0509776102
  30. Maeda, H., Hosokawa, M., Sashima, T, Funayama, K. and Miyashita, K. (2005) Fucoxanthin from edible seaweed, Undaria pinnatifi da, shows antiobesity effect through UCP1 expression in white adipose tissues. Biochem. Biophys. Res. Commun. 332, 392-397. https://doi.org/10.1016/j.bbrc.2005.05.002
  31. Marnett, L. J. (2000) Oxyradicals and DNA damage. Carcinogenesis 21, 361-370. https://doi.org/10.1093/carcin/21.3.361
  32. Mercadante, A. Z. and Egeland, E. S. (2004) Carotenoids with a C40 Skeleton. In Carotenoids-Handbook (G, Britton., S, Liaaen-Jensen., H, Pfander., Eds.), pp. 563. Birkhauser, Basel, Switzerland.
  33. Neofytou, E., Tzortzaki, E. G., Chatziantoniou, A. and Siafakas, N. M. (2012) DNA damage due to oxidative stress in chronic obstructive pulmonary disease (COPD). Int. J. Mol. Sci. 13, 16853-16864. https://doi.org/10.3390/ijms131216853
  34. Nys, K. and Agostinis, P. (2012) Bcl-2 family members: essential players in skin cancer. Cancer Lett. 320, 1-13. https://doi.org/10.1016/j.canlet.2012.01.031
  35. Orrenius, S. (2007) Reactive oxygen species in mitochondria-mediated cell death. Drug Metab. Rev. 39, 443-455. https://doi.org/10.1080/03602530701468516
  36. Perelman, A., Wachtel, C., Cohen, M., Haupt, S., Shapiro, H. and Tzur, A. (2012) JC-1: alternative excitation wavelengths facilitate mitochondrial membrane potential cytometry. Cell Death Dis. 3, 1-7.
  37. Plazar, J., Zegura, B., Lah, T. T. and Filipic, M. (2007) Protective effects of xanthohumol against the genotoxicity of benzo (a) pyrene (BaP), 2-amino-3-methylimidazo [4, 5-f] quinoline (IQ) and tert-butyl hydroperoxide (t-BOOH) in HepG2 human hepatoma cells. Mutat. Res. 632, 1-8. https://doi.org/10.1016/j.mrgentox.2007.03.013
  38. Rajagopalan, R., Ranjan, S. and Nair, C. K. (2003) Effect of vinblastine sulfate on gamma-radiation-induced DNA single-strand breaks in murine tissues. Mutat. Res. 536, 15-25. https://doi.org/10.1016/S1383-5718(03)00015-9
  39. Roberts, C. K. and Sindhu, K. K. (2009) Oxidative stress and metabolic syndrome. Life Sci. 84, 705-712. https://doi.org/10.1016/j.lfs.2009.02.026
  40. Rogakou, E. P., Pilch, D. R., Orr, A. H., Ivanova, V. S. and Bonner, W. M. (1998) DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. J. Biol. Chem. 273, 5858-5868. https://doi.org/10.1074/jbc.273.10.5858
  41. Rosenkranz, A. R., Schmaldienst, S., Stuhlmeier, K. M., Chen, W., Knapp, W. and Zlabinger, G. J. (1992) A microplate assay for the detection of oxidative products using 2′, 7′-dichlorofl uorescin-diacetate. J. Immunol. Methods 156, 39-45. https://doi.org/10.1016/0022-1759(92)90008-H
  42. Sachindra, N. M., Sato, E., Maeda, H., Hosokawa, M., Niwano, Y., Kohno, M. and Miyashita, K. (2007) Radical scavenging and singlet oxygen quenching activity of marine carotenoid fucoxanthin and its metabolites. J. Agric. Food Chem. 55, 8516-8522. https://doi.org/10.1021/jf071848a
  43. Sander, C. S., Chang, H., Salzmann, S., Muller, C. S., Ekanayake-Mudiyanselage, S., Elsner, P. and Thiele, J. J. (2002) Photoaging is associated with protein oxidation in human skin in vivo. J. Invest. Dermatol. 118, 618-625. https://doi.org/10.1046/j.1523-1747.2002.01708.x
  44. Santos, C. X., Anilkumar, N., Zhang, M., Brewer, A. C. and Shah, A. M. (2011) Redox signaling in cardiac myocytes. Free Radic. Biol. Med. 50, 777-793. https://doi.org/10.1016/j.freeradbiomed.2011.01.003
  45. Schumacker, P. T. (2006) Reactive oxygen species in cancer cells: live by the sword, die by the sword. Cancer Cell 10, 175-176. https://doi.org/10.1016/j.ccr.2006.08.015
  46. Sinha, K., Das, J., Pal, P. B. and Sil, P. C. (2013) Oxidative stress: the mitochondria-dependent and mitochondria-independent pathways of apoptosis. Arch. Toxicol. DOI 10.1007/s00204-013-1034- 4. [Epub ahead of print]
  47. Spencer, J. P., Jenner, A., Chimel, K., Aruoma, O. I., Cross, C. E., Wu, R. and Halliwell, B. (1995) DNA strand breakage and base modifi - cation induced by hydrogen peroxide treatment of human respiratory tract epithelial cells. FEBS Lett. 374, 233-236. https://doi.org/10.1016/0014-5793(95)01117-W
  48. Sun Y. (2007) Oxidative stress and cardiac repair/remodeling following infarction. Am. J. Med. Sci. 334, 197-205. https://doi.org/10.1097/MAJ.0b013e318157388f
  49. Woo, M. N., Jeon, S. M., Shin, Y. C., Lee, M. K., Kang, M. and Choi, M. S. (2009) Anti-obese property of fucoxanthin is partly mediated by altering lipid-regulating enzymes and uncoupling proteins of visceral adipose tissue in mice. Mol. Nutr. Food Res. 53, 1603-1611. https://doi.org/10.1002/mnfr.200900079
  50. Yan, X., Chuda, Y., Suzuki, M. and Nagata, T. (1999) Fucoxanthin as the major antioxidant in Hijikia fusiformis, a common edible seaweed. Biosci. Biotechnol. Biochem. 63, 605-607. https://doi.org/10.1271/bbb.63.605

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