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European Journal of Drug Metabolism and Pharmacokinetics

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01.01.2021 | Original Research Article

Impact of Human SULT1E1 Polymorphisms on the Sulfation of 17β-Estradiol, 4-Hydroxytamoxifen, and Diethylstilbestrol by SULT1E1 Allozymes

verfasst von: Amal A. El Daibani, Fatemah A. Alherz, Maryam S. Abunnaja, Ahsan F. Bairam, Mohammed I. Rasool, Katsuhisa Kurogi, Ming-Cheh Liu

Erschienen in: European Journal of Drug Metabolism and Pharmacokinetics | Ausgabe 1/2021

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Abstract

Background and Objectives

Previous studies have revealed that sulfation, as mediated by the estrogen-sulfating cytosolic sulfotransferase (SULT) SULT1E1, is involved in the metabolism of 17β-estradiol (E2), 4-hydroxytamoxifen (4OH-tamoxifen), and diethylstilbestrol in humans. It is an interesting question whether the genetic polymorphisms of SULT1E1, the gene that encodes the SULT1E1 enzyme, may impact on the metabolism of E2 and these two drug compounds through sulfation.

Methods

In this study, five missense coding single nucleotide polymorphisms of the SULT1E1 gene were selected to investigate the sulfating activity of the coded SULT1E1 allozymes toward E2, 4OH-tamoxifen, and diethylstilbestrol. Corresponding cDNAs were generated by site-directed mutagenesis, and recombinant SULT1E1 allozymes were bacterially expressed, affinity-purified, and characterized using enzymatic assays.

Results

Purified SULT1E1 allozymes were shown to display differential sulfating activities toward E2, 4OH-tamoxifen, and diethylstilbestrol. Kinetic analysis revealed further distinct K_m (reflecting substrate affinity) and V_max (reflecting catalytic activity) values of the five SULT1E1 allozymes with E2, 4OH-tamoxifen, and diethylstilbestrol as substrates.

Conclusions

Taken together, these findings highlighted the significant differences in E2-, as well as the drug-sulfating activities of SULT1E1 allozymes, which may have implications in the differential metabolism of E2, 4OH-tamoxifen, and diethylstilbestrol in individuals with different SULT1E1 genotypes.

Nur mit Berechtigung zugänglich

Osborne CK. Tamoxifen in the treatment of breast cancer. N Engl J Med. 1998;339:1609–18. https://doi.org/10.1056/NEJM199811263392207.CrossRefPubMed

Crewe HK, Ellis SW, Lennard MS, Tucker GT. Variable contribution of cytochromes P450 2D6, 2C9 and 3A4 to the 4-hydroxylation of tamoxifen by human liver microsomes. Biochem Pharmacol. 1997;53(2):171–8. https://doi.org/10.1016/s0006-2952(96)00650-8.CrossRefPubMed

Crewe HK, Notley LM, Wunsch RM, Lennard MS, Gillam EM. Metabolism of tamoxifen by recombinant human cytochrome P450 enzymes: formation of the 4-hydroxy, 4′-hydroxy and N-desmethyl metabolites and isomerization of trans-4-hydroxytamoxifen. Drug Metab Dispos. 2002;30(8):869–74. https://doi.org/10.1124/dmd.30.8.869.CrossRefPubMed

Jordan VC, Collins MM, Rowsby L, Prestwich G. A monohydroxylated metabolite of tamoxifen with potent antioestrogenic activity. J Endocrinol. 1977;75(2):305–16. https://doi.org/10.1677/joe.0.0750305.CrossRefPubMed

Chang M. Tamoxifen resistance in breast cancer. Biomol Ther (Seoul). 2012;20(3):256–67. https://doi.org/10.4062/biomolther.2012.20.3.256.CrossRef

Iwase H, Yamamoto Y. Clinical benefit of sequential use of endocrine therapies for metastatic breast cancer. Int J Clin Oncol. 2015;20:253–61. https://doi.org/10.1007/s10147-015-0793-8.CrossRefPubMed

Lonning PE, Taylor PD, Anker G, Iddon J, Wie L, Jorgensen LM, Mella O, Howell A. High-dose estrogen treatment in postmenopausal breast cancer patients heavily exposed to endocrine therapy. Breast Cancer Res Treat. 2001;67:111–6. https://doi.org/10.1023/a:1010619225209.CrossRefPubMed

Mahtani RL, Stein A, Vogel CL. High-dose estrogen as salvage hormonal therapy for highly refractory metastatic breast cancer: a retrospective chart review. Clin Ther. 2009;31:2371–8. https://doi.org/10.1016/j.clinthera.2009.11.002.CrossRefPubMed

de Voogt HJ, Smith PH, Pavone-Macaluso M, de Pauw M, Suciu S. Cardiovascular side effects of diethylstilbestrol, cyproterone acetate, medroxyprogesterone acetate and estramustine phosphate used for the treatment of advanced prostatic cancer: results from European Organization for Research on Treatment of Cancer trials 30761 and 30762. J Urol. 1986;135(2):303–7. https://doi.org/10.1016/s0022-5347(17)45620-5.CrossRefPubMed

10.

Fisher B, Costantino JP, Redmond CK, Fisher ER, Wickerham DL, Cronin WM. Endometrial cancer in tamoxifen-treated breast cancer patients: findings from the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-14. J Natl Cancer Inst. 1994;86(7):527–37. https://doi.org/10.1093/jnci/86.7.527.CrossRefPubMed

11.

Latifyan S, Vansteelandt C, Lecomte S, Efira A. Tamoxifen induced thromboembolic events in breast cancer. Some possible mechanisms. Rev Med Brux. 2017;38(6):494–500.PubMed

12.

Manikandan R, Srirangam SJ, Pearson E, Brown SCW, O'Reilly P, Collins GN. Diethylstilboestrol versus bicalutamide in hormone refractory prostate carcinoma: a prospective randomized trial. Urol Int. 2005;75(3):217–21. https://doi.org/10.1159/000087797.CrossRefPubMed

13.

Nayfield SG, Gorin MB. Tamoxifen-associated eye disease. A review. J Clin Oncol. 1996;14(3):1018–26. https://doi.org/10.1200/JCO.1996.14.3.1018.CrossRefPubMed

14.

Salomao SR, Watanabe SE, Berezovsky A, Motono M. Multifocal electroretinography, color discrimination and ocular toxicity in tamoxifen use. Curr Eye Res. 2007;32(4):345–52. https://doi.org/10.1080/02713680701229638.CrossRefPubMed

15.

Smith DC, Redman BG, Flaherty LE, Li L, Strawderman M, Pienta KJ. A phase II trial of oral diethylstilbesterol as a second-line hormonal agent in advanced prostate cancer. Urology. 1998;52(2):257–60. https://doi.org/10.1016/s0090-4295(98)00173-3.CrossRefPubMed

16.

Falany JL, Pilloff DE, Leyh TS, Falany CN. Sulfation of raloxifene and 4-hydroxytamoxifen by human cytosolic sulfotransferases. Drug Metab Dispos. 2006;34(3):361–8. https://doi.org/10.1124/dmd.105.006551.CrossRefPubMed

17.

Nishiyama T, Ogura K, Nakano H, Ohnuma T, Kaku T, Hiratsuka A, Muro K, Watabe T. Reverse geometrical selectivity in glucuronidation and sulfation of cis- and trans-4-hydroxytamoxifens by human liver UDP-glucuronosyltransferases and sulfotransferases. Biochem Pharmacol. 2002;63(10):1817–30. https://doi.org/10.1016/s0006-2952(02)00994-2.CrossRefPubMed

18.

Suiko M, Sakakibara Y, Liu MC. Sulfation of environmental estrogen-like chemicals by human cytosolic sulfotransferases. Biochem Biophys Res Commun. 2000;267(1):80–4. https://doi.org/10.1006/bbrc.1999.1935.CrossRefPubMed

19.

Falany C, Roth JA. Properties of human cytosolic sulfotransferases involved in drug metabolism. In: Jeffery EH, editor. Human drug metabolism; from molecular biology to man. Boca Raton: CRC; 1993. p. 101–115.

20.

Mulder GJ, Jakoby WB. Sulfation in conjugation reactions. In: Mulder GJ, Jakoby WB, editors. Drug metabolism. London: Taylor and Francis; 1990. p. 107–161.

21.

Weinshilboum R, Otterness D. Sulfotransferase enzymes. In: Kaufmann FC, editor. Conjugation-deconjugation reactions in drug metabolism and toxicity. Berlin: Springer; 1994. p. 45–78.CrossRef

22.

Blanchard RL, Freimuth RR, Buck J, Weinshilboum RM, Coughtrie MW. A proposed nomenclature system for the cytosolic sulfotransferase (SULT) superfamily. Pharmacogenetics. 2004;14(3):199–21111. https://doi.org/10.1097/00008571-200403000-00009.CrossRefPubMed

23.

Freimuth RR, Wiepert M, Chute CG, Wieben ED, Weinshilboum RM. Human cytosolic sulfotransferase database mining: identification of seven novel genes and pseudogenes. Pharmacogenomics J. 2004;4(1):54–655. https://doi.org/10.1038/sj.tpj.6500223.CrossRefPubMed

24.

Falany CN, Krasnykh V, Falany JL. Bacterial expression and characterization of a cDNA for human liver estrogen sulfotransferase. J Steroid Biochem Mol Biol. 1995;52(6):529–39.CrossRefPubMed

25.

Zhang H, Varlamova O, Vargas FM, et al. Sulfuryl transfer: the catalytic mechanism of human estrogen sulfotransferase. J Biol Chem. 1998;273(18):10888–92.CrossRefPubMed

26.

Petrotchenko EV, Doerflein ME, Kakuta Y, et al. Substrate gating confers steroid specificity to estrogen sulfotransferase. J Biol Chem. 1999;274(42):30019–22.CrossRefPubMed

27.

Agarwal N, Alex AB, Farnham JM, Patel S, Gill D, Buckley TH, Stephenson RA, Cannon-Albright L. Inherited variants in SULT1E1 and response to abiraterone acetate by men with metastatic castration refractory prostate cancer. J Urol. 2016;196(4):1112–6. https://doi.org/10.1016/j.juro.2016.04.079.CrossRefPubMed

28.

Choi JY, Lee KM, Park SK, Noh DY, Ahn SH, Chung HW, Han W, Kim JS, Shin SG, Jang IJ, Yoo KY, Hirvonen A, Kang D. Genetic polymorphisms of SULT1A1 and SULT1E1 and the risk and survival of breast cancer. Cancer Epidemiol Biomark Prev. 2005;14(5):1090–5. https://doi.org/10.1158/1055-9965.EPI-04-0688.CrossRef

29.

Cohen S, Laitman Y, Kaufman B, Milgrom R, Nir U, Friedman E. SULT1E1 and ID2 genes as candidates for inherited predisposition to breast and ovarian cancer in Jewish women. Fam Cancer. 2009;8(2):135–44. https://doi.org/10.1007/s10689-008-9218-4.CrossRefPubMed

30.

Daniels J, Kadlubar S. Sulfotransferase genetic variation: from cancer risk to treatment response. Drug Metab Rev. 2013;45(4):415–22. https://doi.org/10.3109/03602532.2013.835621.CrossRefPubMedPubMedCentral

31.

Hirata H, Hinoda Y, Okayama N, Suehiro Y, Kawamoto K, Kikuno N, Rabban JT, Chen LM, Dahiya R. CYP1A1, SULT1A1, and SULT1E1 polymorphisms are risk factors for endometrial cancer susceptibility. Cancer. 2008;112(9):1964–73. https://doi.org/10.1002/cncr.23392.CrossRefPubMed

32.

Rebbeck TR, Troxel AB, Wang Y, Walker AH, Panossian S, Gallagher S, Shatalova EG, Blanchard R, Bunin G, DeMichele A, Rubin SC, Baumgarten M, Berlin M, Schinnar R, Berlin JA, Strom BL. Estrogen sulfation genes, hormone replacement therapy, and endometrial cancer risk. J Natl Cancer Inst. 2006;98(18):1311–20. https://doi.org/10.1093/jnci/djj360.CrossRefPubMed

33.

Woo HI, Lee SK, Kim J, Kim SW, Yu J, Bae SY, Lee JE, Nam SJ, Lee SY. Variations in plasma concentrations of tamoxifen metabolites and the effects of genetic polymorphisms on tamoxifen metabolism in Korean patients with breast cancer. Oncotarget. 2017;8(59):100296–311. https://doi.org/10.18632/oncotarget.22220.CrossRefPubMedPubMedCentral

34.

Yanagisawa K, Sakakibara Y, Suiko M, Takami Y, Nakayama T, Nakajima H, Takayanagi K, Natori Y, Liu MC. cDNA cloning, expression, and characterization of the human bifunctional ATP sulfurylase/adenosine 5′-phosphosulfate kinase enzyme. Biosci Biotechnol Biochem. 1998;62(5):1037–40. https://doi.org/10.1271/bbb.62.1037.CrossRefPubMed

35.

Hui Y, Liu MC. Sulfation of ritodrine by the human cytosolic sulfotransferases (SULTs): Effects of SULT1A3 genetic polymorphism. Eur J Pharmacol. 2015;761:125–9. https://doi.org/10.1016/j.ejphar.2015.04.039.CrossRefPubMedPubMedCentral

36.

Dunbrack RL Jr. Rotamer libraries in the 21st century. Curr Opin Struct Biol. 2002;12(4):431–40. https://doi.org/10.1016/S0959-440X(02)00344-5.CrossRefPubMed

37.

Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE. UCSF Chimera—a visualization system for exploratory research and analysis. J Comput Chem. 2004;25(13):1605–12. https://doi.org/10.1002/jcc.20084.CrossRefPubMed

38.

Mansel R, Goyal A, Nestour EL, Masini-Eteve V, O'Connell K. Afimoxifene Breast Pain Research Group, A phase II trial of Afimoxifene (4-hydroxytamoxifen gel) for cyclical mastalgia in premenopausal women. Breast Cancer Res Treat. 2007;106(3):389–97. https://doi.org/10.1007/s10549-007-9507-x.CrossRefPubMed

39.

Turo R, Tan K, Thygesen H, Sundaram SK, Chahal R, Prescott S, Cross WR. Diethylstilboestrol (1 mg) in the management of castration-resistant prostate cancer. Urol Int. 2015;94(3):307–12. https://doi.org/10.1159/000365198.CrossRefPubMed

40.

Falany JL, Falany CN. Expression of cytosolic sulfotransferases in normal mammary epithelial cells and breast cancer cell lines. Cancer Res. 1996;56(7):1551–5.PubMed

41.

Nakamura Y, Suzuki T, Fukuda T, Ito A, Endo M, Moriya T, Arai Y, Sasano H. Steroid sulfatase and estrogen sulfotransferase in human prostate cancer. Prostate. 2006;66(9):1005–122. https://doi.org/10.1002/pros.20426.CrossRefPubMed

42.

Qian Y, Deng C, Song WC. Expression of estrogen sulfotransferase in MCF-7 cells by cDNA transfection suppresses the estrogen response: potential role of the enzyme in regulating estrogen-dependent growth of breast epithelial cells. J Pharmacol Exp Ther. 1998;286(1):555–60.PubMed

43.

Hui Y, Luo L, Zhang L, Kurogi K, Zhou C, Sakakibara Y, Suiko M, Liu MC. Sulfation of afimoxifene, endoxifen, raloxifene, and fulvestrant by the human cytosolic sulfotransferases (SULTs): a systematic analysis. J Pharmacol Sci. 2015;128(3):144–9. https://doi.org/10.1016/j.jphs.2015.06.004.CrossRefPubMed

44.

Areepium N, Panomvana D, Rungwanonchai P, Sathaporn S, Voravud N. Effects of CYP2D6 and UGT2B7 polymorphisms on pharmacokinetics of tamoxifen in Thai breast cancer patients. Breast Cancer (Dove Med Press). 2013;5:73–8. https://doi.org/10.2147/BCTT.S47172.CrossRef

45.

de Vries Schultink AH, Zwart W, Linn SC, Beijnen JH, Huitema AD. Effects of pharmacogenetics on the pharmacokinetics and pharmacodynamics of tamoxifen. Clin Pharmacokinet. 2015;54(8):797–810. https://doi.org/10.1007/s40262-015-0273-3.CrossRefPubMedPubMedCentral

46.

Fernandez-Santander A, Gaibar M, Novillo A, Romero-Lorca A, Rubio M, Chicharro LM, Tejerina A, Bandres F. Relationship between genotypes Sult1a2 and Cyp2d6 and tamoxifen metabolism in breast cancer patients. PLoS ONE. 2013;8(7):e70183. https://doi.org/10.1371/journal.pone.0070183.CrossRefPubMedPubMedCentral

47.

Gjerde J, Hauglid M, Breilid H, Lundgren S, Varhaug JE, Kisanga ER, Mellgren G, Steen VM, Lien EA. Effects of CYP2D6 and SULT1A1 genotypes including SULT1A1 gene copy number on tamoxifen metabolism. Ann Oncol. 2008;19(1):56–61. https://doi.org/10.1093/annonc/mdm434.CrossRefPubMed

48.

Lim JS, Chen XA, Singh O, Yap YS, Ng RC, Wong NS, Wong M, Lee EJ, Chowbay B. Impact of CYP2D6, CYP3A5, CYP2C9 and CYP2C19 polymorphisms on tamoxifen pharmacokinetics in Asian breast cancer patients. Br J Clin Pharmacol. 2011;71(5):737–50. https://doi.org/10.1111/j.1365-2125.2011.03905.x.CrossRefPubMedPubMedCentral

49.

Murdter TE, Schroth W, Bacchus-Gerybadze L, Winter S, Heinkele G, Simon W, Fasching PA, Fehm T, German Tamoxifen, and AI Clinician Group, Eichelbaum M, Schwab M, Brauch H. Activity levels of tamoxifen metabolites at the estrogen receptor and the impact of genetic polymorphisms of phase I and II enzymes on their concentration levels in plasma. Clin Pharmacol Ther. 2011;89(5):708–17. https://doi.org/10.1038/clpt.2011.27.CrossRefPubMed

50.

Zafra-Ceres M, de Haro T, Farez-Vidal E, Blancas I, Bandres F, de Duenas EM, Ochoa-Aranda E, Gomez-Capilla JA, Gomez-Llorente C. Influence of CYP2D6 polymorphisms on serum levels of tamoxifen metabolites in Spanish women with breast cancer. Int J Med Sci. 2013;10(7):932–7. https://doi.org/10.7150/ijms.5708.CrossRefPubMedPubMedCentral

51.

Adjei AA, Thomae BA, Prondzinski JL, Eckloff BW, Wieben ED, Weinshilboum RM. Human estrogen sulfotransferase (SULT1E1) pharmacogenomics: gene resequencing and functional genomics. Br J Pharmacol. 2003;139(8):1373–82. https://doi.org/10.1038/sj.bjp.0705369.CrossRefPubMedPubMedCentral

52.

Pedersen LC, Petrotchenko E, Shevtsov S, Negishi M. Crystal structure of the human estrogen sulfotransferase-PAPS complex: evidence for catalytic role of Ser137 in the sulfuryl transfer reaction. J Biol Chem. 2002;277(20):17928–32. https://doi.org/10.1074/jbc.M111651200.CrossRefPubMed

53.

Shevtsov S, Petrotchenko EV, Pedersen LC, Negishi M. Crystallographic analysis of a hydroxylated polychlorinated biphenyl (OH-PCB) bound to the catalytic estrogen binding site of human estrogen sulfotransferase. Environ Health Perspect. 2003;111(7):884–8. https://doi.org/10.1289/ehp.6056.CrossRefPubMedPubMedCentral

54.

Thomas MP, Potter BV. The structural biology of oestrogen metabolism. J Steroid Biochem Mol Biol. 2013;137:27–49. https://doi.org/10.1016/j.jsbmb.2012.12.014.CrossRefPubMedPubMedCentral

55.

Kakuta Y, Pedersen LG, Carter CW, Negishi M, Pedersen LC. Crystal structure of estrogen sulphotransferase. Nat Struct Biol. 1997;4(11):904–8. https://doi.org/10.1038/nsb1197-904.CrossRefPubMed

56.

Petrotchenko EV, Pedersen LC, Borchers CH, Tomer KB, Negishi M. The dimerization motif of cytosolic sulfotransferases. FEBS Lett. 2001;490:39–433. https://doi.org/10.1016/s0014-5793(01)02129-9.CrossRefPubMed

57.

Cook I, Wang T, Almo SC, Kim J, Falany CN, Leyh TS. The gate that governs sulfotransferase selectivity. Biochemistry. 2012;52(2):415–24. https://doi.org/10.1021/bi301492j.CrossRefPubMed

58.

Tibbs ZE, Rohn-Glowacki KJ, Crittenden F, Guidry AL, Falany CN. Structural plasticity in the human cytosolic sulfotransferase dimer and its role in substrate selectivity and catalysis. Drug Metab Pharmacokinet. 2015;30(1):3–20. https://doi.org/10.1016/j.dmpk.2014.10.004.CrossRefPubMed

Titel: Impact of Human SULT1E1 Polymorphisms on the Sulfation of 17β-Estradiol, 4-Hydroxytamoxifen, and Diethylstilbestrol by SULT1E1 Allozymes
verfasst von: Amal A. El Daibani
Fatemah A. Alherz
Maryam S. Abunnaja
Ahsan F. Bairam
Mohammed I. Rasool
Katsuhisa Kurogi
Ming-Cheh Liu
Publikationsdatum: 01.01.2021
Verlag: Springer International Publishing
Erschienen in: European Journal of Drug Metabolism and Pharmacokinetics / Ausgabe 1/2021
Print ISSN: 0378-7966
Elektronische ISSN: 2107-0180
DOI: https://doi.org/10.1007/s13318-020-00653-1

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

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Impact of Human SULT1E1 Polymorphisms on the Sulfation of 17β-Estradiol, 4-Hydroxytamoxifen, and Diethylstilbestrol by SULT1E1 Allozymes

Abstract

Background and Objectives

Methods

Results

Conclusions

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Abstract

Background and Objectives

Methods

Results

Conclusions

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