DOI QR코드

DOI QR Code

Modulation of Cytotoxic Effects of Resveratrol by Its Anti- or Pro-oxidant Properties

Resveratrol의 항산화 및 산화촉진 활성이 세포독성에 미치는 영향

  • Received : 2010.10.25
  • Accepted : 2010.11.19
  • Published : 2011.02.28

Abstract

Resveratrol is a polyphenolic compound frequently found in the diet, and its physiological actions have been extensively investigated. In the present study, modulation of the antioxidant and cytotoxic properties of resveratrol at different pHs by various antioxidants were investigated. To measure its antioxidant effects, resveratrol was incubated at different pHs, including 6.5, 7.4, and 8.0. Resveratrol incubated at pH 6.5 showed significantly higher DPPH radical scavenging activity, whereas resveratrol incubated at pH 8.0 did not show antioxidant effects. Resveratrol produced much higher amounts of $H_2O_2$ at pH 8.0 than 7.4. The cytotoxic effects of resveratrol on HeLa cells were significantly enhanced by several antioxidants, including superoxide dismutase, N-acetyl cysteine, glutathione, and ascorbic acid. The present results suggest that resveratrol shows anti- or pro-oxidant effects in different cellular organelles according to the pH conditions, and blocking of reactive oxygen species from resveratrol enhances its cytotoxic effects.

Keywords

resveratrol;antioxidant;prooxidant;cytotoxicity;reactive oxygen species

References

  1. Kopp P. Resveratrol, a phytoestrogen found in red wine. A possible explanation for the conundrum of the 'French paradox'. Eur. J. Endocrinol. 138: 619-620 (1998) https://doi.org/10.1530/eje.0.1380619
  2. Soleas GJ, Diamandis EP, Goldberg DM. Resveratrol: A molecule whose time has come? and gone? Clin. Biochem. 30: 91-113 (1997) https://doi.org/10.1016/S0009-9120(96)00155-5
  3. Lobo RA. Benefits and risks of estrogen replacement therapy 1. Obstet. Gynecol. 173: 982-989 (1995) https://doi.org/10.1016/0002-9378(95)90247-3
  4. Gehm BD, McAndrews JM, Chien PY, Jameson JL. Resveratrol, a polyphenolic compound found in grapes and wine, is an agonist for the estrogen receptor. Proc. Natl. Acad. Sci. USA 94: 14138-14143 (1997) https://doi.org/10.1073/pnas.94.25.14138
  5. Bhat KPL, Pezzuto JM. Resveratrol exhibits cytostatic and antiestrogenic properties with human endometrial adenocarcinoma (Ishikawa) cells. Cancer Res. 61: 6137-6144 (2001)
  6. Holmes-McNary M, Baldwin AS. Chemopreventive properties of trans-resveratrol are associated with inhibition of activation of the $I{\kappa}B$ kinase. Cancer Res. 60: 3477-3483 (2000)
  7. Jang M, Cai L, Udeani GO, Slowing KV, Thomas CF, Beecher CWW, Fong HHS, Farnsworth NR, Kinghorn AD, Mehta RG. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science 275: 218-220 (1997) https://doi.org/10.1126/science.275.5297.218
  8. Frankel E, Parks E, Xu R, Schneeman B, Davis P, German J. Effect of n-3 fatty acid-rich fish oil supplementation on the oxidation of low density lipoproteins. Lipids 29: 233-236 (1994) https://doi.org/10.1007/BF02536326
  9. Bertelli AA, Giovannini L, Giannessi D, Migliori M, Bernini W, Fregoni M, Bertelli A. Antiplatelet activity of synthetic and natural resveratrol in red wine. Int. J. Tissue React. 17: 1-3 (1995)
  10. Stojanovi S, Sprinz H, Brede O. Efficiency and mechanism of the antioxidant action of trans-resveratrol and its analogues in the radical liposome oxidation. Arch. Biochem. Biophys. 391: 79-89 (2001) https://doi.org/10.1006/abbi.2001.2388
  11. Murcia MA, Martinez-Tome M. Antioxidant activity of resveratrol compared with common food additives. J. Food Protect. 64: 379-384 (2001)
  12. Mahal H, Mukherjee T. Scavenging of reactive oxygen radicals by resveratrol: Antioxidant effect. Res. Chem. Intermediat. 32:59-71 (2006) https://doi.org/10.1163/156856706775012941
  13. Martinez J, Moreno JJ. Effect of resveratrol, a natural polyphenolic compound, on reactive oxygen species and prostaglandin production. Biochem. Pharmacol. 59: 865-870 (2000) https://doi.org/10.1016/S0006-2952(99)00380-9
  14. Gusman J, Malonne H, Atassi G. A reappraisal of the potential chemopreventive and chemotherapeutic properties of resveratrol. Carcinogenesis 22: 1111-1117 (2001) https://doi.org/10.1093/carcin/22.8.1111
  15. Ahmad KA, Clement V, Pervaiz S. Pro-oxidant activity of low doses of resveratrol inhibits hydrogen peroxide-induced apoptosis. Ann. NY Acad. Sci. 1010: 365-373 (2003) https://doi.org/10.1196/annals.1299.067
  16. Alarcon de la Lastra C, Villegas I. Resveratrol as an antioxidant and pro-oxidant agent: Mechanisms and clinical implications. Biochem. Soc. T. 35: 1156-1160 (2007) https://doi.org/10.1042/BST0351156
  17. Blois MS. Antioxidant determinations by the use of a stable free radical. Nature 26: 1699-1203 (1958)
  18. Waslidge NB, Hayes DJ. A colorimetric method for the determination of lipoxygenase activity suitable for use in a high throughput assay format. Anal. Biochem. 231: 354-358 (1995) https://doi.org/10.1006/abio.1995.0063
  19. Zini R, Morin C, Bertelli A, Bertelli AA, Tillement JP. Effects of resveratrol on the rat brain respiratory chain. Drug Exp. Clin. Res. 25: 87-97 (1999)
  20. Leonard SS, Xia C, Jiang BH, Stinefelt B, Klandorf H, Harris GK, Shi X. Resveratrol scavenges reactive oxygen species and effects radical-induced cellular responses. Biochem. Bioph. Res. Co. 309: 1017-1026 (2003) https://doi.org/10.1016/j.bbrc.2003.08.105
  21. Losa G. Resveratrol modulates apoptosis and oxidation in human blood mononuclear cells. Eur. J. Clin. Invest. 33: 818-823 (2003) https://doi.org/10.1046/j.1365-2362.2003.01219.x
  22. Juan ME, Wenzel U, Daniel H, Planas JM. Resveratrol induces apoptosis through ROS-dependent mitochondria pathway in HT- 29 human colorectal carcinoma cells. J. Agr. Food Chem. 56: 4813-4818 (2008) https://doi.org/10.1021/jf800175a
  23. Ozgova S, Hermanek J, Gut I. Different antioxidant effects of polyphenols on lipid peroxidation and hydroxyl radicals in the NADPH-, Fe-ascorbate-and Fe-microsomal systems. Biochem. Pharmacol. 66: 1127-1137 (2003) https://doi.org/10.1016/S0006-2952(03)00425-8
  24. Demaurex N. pH homeostasis of cellular organelles. News Physiol. Sci. 17: 1-5 (2002)
  25. Boonstra J, Post JA. Molecular events associated with reactive oxygen species and cell cycle progression in mammalian cells. Gene 337: 1-13 (2004) https://doi.org/10.1016/j.gene.2004.04.032
  26. Hou Z, Sang S, You H, Lee MJ, Hong J, Chin KV, Yang CS. Mechanism of action of (-)-epigallocatechin-3-gallate: Auto-oxidation- dependent inactivation of epidermal growth factor receptor and direct effects on growth inhibition in human esophageal cancer KYSE 150 cells. Cancer Res. 65: 8049-8056 (2005)

Acknowledgement

Supported by : 서울여자대학교