본문 바로가기
KERD
논문KCI 등재

Modulatory effects of α- and γ-tocopherols on 4-hydroxyestradiol induced oxidative stresses in MCF-10A breast epithelial cells

2

조회

0

다운로드

1

인용

0

참고문헌

키워드

초록

The elevated level of circulating estradiol increases the risk of breast tumor development. To gain further insight into mechanisms involved in their actions, we investigated the molecular mechanisms of 4-hydroxyestradiol (4-OHE2) to initiate and/or promote abnormal cell growth, and of α- or γ-tocopherol to inhibit this process. MCF-10A, human breast epithelial cells were incubated with 0.1 μM 4-OHE2, either with or without 30 μM tocopherols for 96 h. 4-OHE2 caused the accumulation of intracellular ROS, while cellular GSH/GSSG ratio and MnSOD protein levels were decreased, indicating that there was an oxidative burden. 4-OHE2 treatment also changed the levels of DNA repair proteins, BRCA1 and PARP-1. γ-Tocopherol suppressed the 4-OHE2-induced increases in ROS, GSH/GSSG ratio, and MnSOD protein expression, while α-tocopherol up-regulated BRCA1 and PARP-1 protein expression. In conclusion, 4-OHE2 increases oxidative stress reducing the level of proteins related to DNA repair. Tocopherols suppressed oxidative stress by scavenging ROS or up-regulating DNA repair elements.

Abstract

The elevated level of circulating estradiol increases the risk of breast tumor development. To gain further insight into mechanisms involved in their actions, we investigated the molecular mechanisms of 4-hydroxyestradiol (4-OHE2) to initiate and/or promote abnormal cell growth, and of α- or γ-tocopherol to inhibit this process. MCF-10A, human breast epithelial cells were incubated with 0.1 μM 4-OHE2, either with or without 30 μM tocopherols for 96 h. 4-OHE2 caused the accumulation of intracellular ROS, while cellular GSH/GSSG ratio and MnSOD protein levels were decreased, indicating that there was an oxidative burden. 4-OHE2 treatment also changed the levels of DNA repair proteins, BRCA1 and PARP-1. γ-Tocopherol suppressed the 4-OHE2-induced increases in ROS, GSH/GSSG ratio, and MnSOD protein expression, while α-tocopherol up-regulated BRCA1 and PARP-1 protein expression. In conclusion, 4-OHE2 increases oxidative stress reducing the level of proteins related to DNA repair. Tocopherols suppressed oxidative stress by scavenging ROS or up-regulating DNA repair elements.

참고문헌 (51)

  1. Abiaka C, "Plasma concentrations of alpha-tocopherol and urate in patients with different types of cancer", J Clin Pharm Ther, 26, pp.265~270 (2001)
  2. Aiub CA, "DNA-repair genes and vitamin E in the prevention of N-nitrosodiethylamine mutagenicity", Cell Biol Toxicol, 25, pp.393~402 (2009)
  3. Ame JC, "The PARP superfamily", Bioessays, 26, pp.882~893 (2004)
  4. Arrigo AP, "Gene expression and the thiol redox state", Free Radic Biol Med, 27, pp.936~944 (1999)
  5. Baba T, "Estrogen, insulin, and dietary signals cooperatively regulate longevity signals to enhance resistance to oxidative stress in mice", J Biol Chem, 280, pp.16417~16426 (2005)
  6. Bae I, "BRCA1 induces antioxidant gene expression and resistance to oxidative stress", Cancer Res, 64, pp.7893~7909 (2004)
  7. Belous AR, "Cytochrome P450 1B1-mediated estrogen metabolism results in estrogen-deoxyribonucleoside adduct formation", Cancer Res, 67, pp.812~817 (2007)
  8. Brodie SG, "BRCA1-associated tumorigenesis: what have we learned from knockout mice?", Trends Genet, 17, pp.S18~22 (2001)
  9. Campbell SE, "Comparative effects of RRR-alpha- and RRR-gamma-tocopherol on proliferation and apoptosis in human colon cancer cell lines", BMC Cancer, 6, pp.13~ (2006)
  10. Campbell SE, "Gamma (gamma) tocopherol upregulates peroxisome proliferator activated receptor (PPAR) gamma (gamma) expression in SW 480 human colon cancer cell lines", BMC Cancer, 3, pp.25~ (2003)
  11. Cantor SB, "Assessing the link between BACH1 and BRCA1 in the FA pathway", Cell Cycle, 5, pp.164~167 (2006)
  12. Chen ZH, "4-Hydroxyestradiol induces oxidative stress and apoptosis in human mammary epithelial cells: possible protection by NF-kappaB and ERK", MAPK, 2005, pp.208, 46~56
  13. Colditz GA, "Relationship between estrogen levels, use of hormone replacement therapy, and breast cancer", J Natl Cancer Inst, 90, pp.814~823 (1998)
  14. Cuendet M, "Response of human mammary epithelial cells to DNA damage induced by 4-hydroxyequilenin: Lack of p53-mediated G1 arrest", Chem Biol Interact, 161, pp.271~278 (2006)
  15. de Murcia G, "Poly (ADP-ribose) polymerase: a molecular nick-sensor", Trends Biochem Sci, 19, pp.172~176 (1994)
  16. De Soto JA, "PARP-a inhibitor: are they the long-sought genetically specific drugs for BRCA1", 2-associated breast cancer?, 2006, pp.3, 117~123
  17. Deng CX, "Roles of BRCA1 in DNA damage repair: a link between development and cancer", Hum Mol Genet, 12(Spec 1), pp.R113~R123 (2003)
  18. Esworthy RS, "Expression of seleniumdependent glutathione peroxidase in human breast tumor cell lines", Cancer Res, 55, pp.957~962 (1995)
  19. Fernandez SV, "Estradiol and its metabolites 4-hydroxyestradiol and 2-hydroxyestradiol induce mutation in human breast epithelial cells", Int J Cancer, 118, pp.1862~1868 (2006)
  20. Ginestier C, "Getting to the root of BRCA1-deficient breast cancer", Cell Stem Cell, 5, pp.229~330 (2009)
  21. Goodman GE, "The association between lung and prostate cancer risk, and serum micronutrients: results and lessons learned from beta-carotene and retinol efficacy trial", Cancer Epidemiol Biomarkers Prev, 12, pp.518~526 (2003)
  22. Griffith OW, "Determination of glutathione and glutathione disulfide using glutathione reductase and 2-vinylpyridine", Anal Biochem, 106, pp.207~212 (1980)
  23. Grodstein F, "Postmenopausal hormone therapy and mortality", N Engl J Med, 336, pp.1769~1775 (1997)
  24. Gu X, "Vitamin E succinate induces ceramide-mediated apoptosis in head and neck squamous cell carcinoma in vitro and in vivo", Clin Cancer Res, 14, pp.1840~1848 (2008)
  25. Gysin R, "Gamma-tocopherol inhibits human cancer cell cycle progression and cell proliferation by down-regulation of cyclins", FASEB J, 16, pp.1952~1954 (2002)
  26. Han X, "8-Hydroxylation of guanine bases in kidney and liver DNA of hamsters treated with estradiol: role of free radicals in estrogen-induced carcinogenesis", Cancer Res, 54, pp.5515~5517 (1994)
  27. Harvell DM, "Rat strain-specific actions of 17beta-estradiol in the mammary gland: correlation between estrogen-induced lobuloalveolar hyperplasia and susceptibility to estrogen-induced mammary cancers", Proc Nat Acad Sci U S A, 97, pp.2779~2784 (2000)
  28. Hitchler MJ, "Epigenetic regulation of manganese superoxide dismutase expression in human breast cancer cells", Epigenetics, 1, pp.163~171 (2006)
  29. Jiang LJQ, "Gamma-tocopherol supplementation inhibits protien nitration and ascorbate oxidation in rats with inflammation", Free Rad Biol Med, 33, pp.1534~1542 (2002)
  30. King MC, "Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2", Science, 302, pp.643~646 (2003)
  31. Lane DP, "Cancer in guardian of the genome", Nature, 358, pp.15~16 (1992)
  32. Li D, "Relative Effects of alpha- and gamma-Tocopherol on Low-Density Lipoprotein Oxidation and Superoxide Dismutase and Nitric Oxide Synthase Activity and Protein Expression in Rats", J Cardiovasc Pharmacol Ther, 4, pp.219~226 (1999)
  33. Li JJ, "Inhibition of AP-1 and NF-kappaB by manganese-containing superoxide dismutase in human breast cancer cells", FASEB J, 12, pp.1713~1723 (1998)
  34. Liu R, "Transfection and expression of MnSOD cDNA decreases tumor malignancy of human oral squamous carcinoma SCC-25 cells", Hum Gene Ther, 8, pp.585~595 (1997)
  35. Liu R, "Effects of endothelial nitric oxide synthase gene expression on the tumor biology of human oral carcinoma SCC-25 cells", Cell Growth Differ, 9, pp.239~246 (1998)
  36. Malkin D, "Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms", Science, 250, pp.1233~1238 (1990)
  37. McMillan DC, "The relationship between reduced vitamin antioxidant concentrations and the systemic inflammatory response in patients with common solid tumours", Clin Nutr, 21, pp.161~164 (2002)
  38. Mense SM, "Vitamin C and alpha-naphthoflavone prevent estrogen-induced mammary tumors and decrease oxidative stress in female ACI rats", Carcinogenesis, 30, pp.1202~1208 (2009)
  39. Pastore A, "Analysis of glutathione: Implication in redox and detoxification", Clin Chim Acta, 333, pp.19~39 (2003)
  40. Plummer ER, "Inhibition of poly (ADP-ribose) polymerase in cancer", Curr Opin Pharmacol, 6, pp.364~368 (2006)
  41. Rosen EM, "BRCA1 gene in breast cancer", J Cell Physiol, 196, pp.19~41 (2003)
  42. Roy S, "Vitamin E sensitive genes in the developing rat fetal brain: a high-density oligonucleotide microarray analysis", FEBS Lett, 530, pp.17~23 (2002)
  43. Service RF, "New role for estrogen in cancer?", Science, 279, pp.1631~1633 (1998)
  44. Theriault A, "Tocotrienol: a review of its therapeutic potential", Clin Biochem, 32, pp.309~319 (1999)
  45. Tong WM, "Poly (ADP-ribose) polymerase-1 plays a role in suppressing mammary tumorigenesis in mice", Oncogene, 26, pp.3857~3867 (2007)
  46. Venkitaraman AR, "Cancer susceptibility and the functions of BRCA1 and BRCA2", Cell, 108, pp.171~182 (2002)
  47. Walsh T, "Spectrum of mutations in BRCA1, BRCA2, CHEK2, and TP53 in Families at high risk of breast cancer", JAMA, 295, pp.1379~1388 (2007)
  48. Wittmann BM, "The breast cell growth inhibitor, estrogen down regulated gene 1, modulates a novel functional interaction between estrogen receptor alpha and transcriptional elongation factor cyclin T1", Oncogene, 24, pp.5576~5588 (2005)
  49. Yager JD, "Molecular mechanisms of estrogen carcinogenesis", Annu Rev Pharmacol Toxicol, 36, pp.203~232 (1996)
  50. Yu W, "RRR-alpha-tocopheryl succinate-induced apoptosis of human breast cancer cells involves Bax translocation to mitochondria", Cancer Res, 63, pp.2483~2491 (2003)
  51. Zhang J, "The role of the BRCA1 tumor suppressor in DNA double-strand break repair", Mol Cancer Res, 3, pp.531~539 (2005)

관련 논문AI추천

이 간행물의 다른 논문 (11건)