Food Science and Biotechnology

Korean Society of Food Science and Technology (한국식품과학회)
권호 표지

Potent HAT Inhibitory Effect of Aqueous Extract from Bellflower (Platycodon grandiflorum) Roots on Androgen Receptor-mediated Transcriptional Regulation

  • Lee, Yoo-Hyun (Department of Biochemistry and Molecular Biology, Center for Chronic Metabolic Disease Research, College of Medicine, Yonsei University) ;
  • Kim, Yong-Jun (Department of Food and Biotechnology, Korea University) ;
  • Kim, Ha-Il (Department of Biochemistry and Molecular Biology, Center for Chronic Metabolic Disease Research, College of Medicine, Yonsei University) ;
  • Cho, Hong-Yon (Department of Food and Biotechnology, Korea University) ;
  • Yoon, Ho-Geun (Department of Biochemistry and Molecular Biology, Center for Chronic Metabolic Disease Research, College of Medicine, Yonsei University)
  • Published : 2007.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

Histone acetyltransferase (HAT) is a family of enzymes that regulate histone acetylation. Dysfunction of HAT plays a critical role in the development of cancer. Here we have screened the various plant extracts to find out the potent HAT inhibitors. The bellflower (Platycodon grandiflorum) root have exhibited approximately 30% of the inhibitory effects on HAT activity, especially p300 and CBP (CREB-binding protein) at the concentration of $100\;{\mu}g/mL$. The cell viability was decreased approximately 52% in LNCaP cell for 48 hr incubation. Furthermore, mRNA level of 3 androgen receptor target genes, PSA, NKX3.1, and TSC22 were decreased with bellflower root extract treatment ($100\;{\mu}g/mL$) in the presence of androgen. In ChIP assay, the acetylation of histone H3 and H4 in PSA promoter region was dramatically repressed by bellflower root treatment, but not TR target gene, Dl. Therefore, the potent HAT inhibitory effect of bellflower root led to the decreased transcription of AR target genes and prostate cancer cell growth with the repression of histone hyperacetylation.

Keywords

References

  1. Park SK, Sakoda LC, Kang D, Chokkalingam AP, Lee E, Shin HR., Ahn YO, Shin MH, Lee CW, Lee DH, Blair A, Devesa SS, Hsing AW. Rising prostate cancer rates in South Korea. Prostate 66: 1285-1291 (2006) https://doi.org/10.1002/pros.20419
  2. Lee HS, Kim EJ, Cho JS , Cho HJ, Lee SK, Jung KC, Yoon Park JB. Conjugated linoleic acid decreases phosphorylated akt levels in Mat-LyLu (MLL) rat prostate cancer cells. Food Sci. Biotechnol. 13: 353-357 (2004)
  3. Taplin ME, Balk SP. Androgen receptor: a key molecule in the progression of prostate cancer to hormone independence. J. Cell Biochem. 15: 483-490 (2004)
  4. Chen L, Meng S, Wang H, Bali P, Bai W, Li B, Atadja P, Bhalla KN, Wu J. Chemical ablation of androgen receptor in prostate cancer cells by the histone deacetylase inhibitor LAQ824. Mol. Cancer Ther. 4: 1311-1319 (2005) https://doi.org/10.1158/1535-7163.MCT-04-0287
  5. Yoon HG, Wong J. The corepressors silencing mediator of retinoid and thyroid hormone receptor and nuclear receptor corepressor are involved in agonist- and antagonist-regulated transcription by androgen receptor. Mol. Endocrinol. 20: 1048-1060 (2006) https://doi.org/10.1210/me.2005-0324
  6. Fu M, Rao M, Wang C, Sakamaki T, Wang J, Di Vizio D, Zhang X, Albanese C, Balk S, Chang C, Fan S, Rosen E, Palvimo JJ, Janne OA, Muratoglu S, Avantaggiati ML, Pestell RG. Acetylation of androgen receptor enhances coactivator binding and promotes prostate cancer cell growth. Mol. Cell Biol. 23: 8563-8575 (2003) https://doi.org/10.1128/MCB.23.23.8563-8575.2003
  7. Fu M, Wang C, Zhang X, Pestell RG. Acetylation of nuclear receptors in cellular growth and apoptosis. Biochem. Pharmacol. 68: 1199-2108 (2004) https://doi.org/10.1016/j.bcp.2004.05.037
  8. Kang J, Chen J, Shi Y, Jia J, Zhang Y. Curcumin-induced histone hypoacetylation: the role of reactive oxygen species. Biochem. Pharmacol. 69: 1205-1213 (2005) https://doi.org/10.1016/j.bcp.2005.01.014
  9. Stimson L, Rowlands MG, Newbatt YM, Smith NF, Raynaud FI, Rogers P, Bavetsias V, Gorsuch S, Jarman M, Bannister A, Kouzarides T, McDonald E, Workman P, Aherne GW, Isothiazolones as inhibitors of PCAF and p300 histone acetyltransferase activity. Mol. Cancer Ther. 4: 1521-1532 (2005) https://doi.org/10.1158/1535-7163.MCT-05-0135
  10. Balasubramanyam K, Varier RA, Altaf M, Swaminathan V, Siddappa NB, Ranga U, Kundu TK. Curcumin, a novel p300/ CREB-binding protein-specific inhibitor of acetyltransferase, represses the acetylation of histone/nonhistone proteins and histone acetyltransferase-dependent chromatin transcription. J. Biol. Chem. 279: 51163-51171 (2004) https://doi.org/10.1074/jbc.M409024200
  11. Druesne N, Pagniez A, Mayeur C, Thomas M, Cherbuy C, Duee PH, Martel P, Chaumontet C. Diallyl disulfide (DADS) increases histone acetylation and p21 (waf1/cip1) expression in human colon tumor cell lines. Carcinogenesis 25: 1227-1236 (2004) https://doi.org/10.1093/carcin/bgh123
  12. Inche AG, La Thangue NB. Chromatin control and cancer-drug discovery: realizing the promise. Drug Discov. Today 11: 97-109 (2006) https://doi.org/10.1016/S1359-6446(05)03691-3
  13. Lau OD, Kundu TK, Soccio RE, Ait-Si-Ali S, Khalil EM, Vassilev A, Wolffe AP, Nakatani Y, Roeder RG, Cole PA. HATs off: selective synthetic inhibitors of the histone acetyltransferases p300 and PCAP. Mol. Cell. 5: 589-595 (2000) https://doi.org/10.1016/S1097-2765(00)80452-9
  14. Balasubramanyam K, Altaf M, Varier RA, Swaminathan V, Ravindran A, Sadhale PP, Kundu TK. Polyisoprenylated benzophenone, garcinol, a natural histone acetyltransferase inhibitor, represses chromatin transcription and alters global gene expression. J. Biol. Chem. 279: 33716-33726 (2004) https://doi.org/10.1074/jbc.M402839200
  15. Sun Y, Jiang X, Chen S, Price BD. Inhibition of histone acetyltransferase activity by anacardic acid sensitizes tumor cells to ionizing radiation. FEBS Lett. 580: 4353-4356 (2006) https://doi.org/10.1016/j.febslet.2006.06.092
  16. Lee KJ, Kim JY, Choi JH, Kim HG, Chung YC, Roh SH, Jeong HG. Inhibition of tumor invasion and metastasis by aqueous extract of the radix of Plalycodon grandiflorum. Food Chem. Toxicol. 44: 1890-1896 (2006) https://doi.org/10.1016/j.fct.2006.06.009
  17. Kim YS, Kim JS, Choi SU, Kim JS, Lee HS, Roh SH, Jeong YC, Kim YK, Ryu SY. Isolation of a new saponin and cytotoxic effect of saponins from the root of Platycodon grandiflorum on human tumor cell lines. Planta Med. 71: 566-568 (2005) https://doi.org/10.1055/s-2005-864161
  18. Park DI, Lee JH, Moon SK, Kim CH, Lee YT, Cheong J, Choi BT, Choi YH. Induction of apoptosis and inhibition of telomerase activity by aqueous extract from Platycodon grandiflorum in human lung carcinoma cells. Pharmacol. Res. 51: 437-443 (2005) https://doi.org/10.1016/j.phrs.2004.11.003
  19. Lee JY, Hwang WI, Lim ST. Antioxidant and anticancer activities of organic extracts from Platycodon grandiflorum A. De Candolle roots. J. Ethnopharmacol. 93: 409-415 (2004) https://doi.org/10.1016/j.jep.2004.04.017
  20. Yoon HG, Chan DW, Huang ZQ, Li J, Fondell JD, Qin J, Wong J. Purification and functional characterization of the human N-CoR complex: the roles of HDAC3, TBL1, and TBLR1. EMBO J. 22: 1336-1346 (2003) https://doi.org/10.1093/emboj/cdg120
  21. Heinlein CA, Chang C. Androgen receptor in prostate cancer. Endocr. Rev. 25: 276-308 (2004) https://doi.org/10.1210/er.2002-0032
  22. Kim J, Coetzee GA. Prostate specific antigen gene regulation by androgen receptor. J. Cell Biochem. 93: 233-241 (2004) https://doi.org/10.1002/jcb.20228
  23. Yoon HG, Chan DW, Reynolds AB, Qin J, Wong J. N-CoR mediates DNA methylation-dependent repression through a methyl CpG binding protein Kaiso. Mol. Cell. 12: 723-734 (2003) https://doi.org/10.1016/j.molcel.2003.08.008
  24. Shang Y, Hu X, DiRenzo J, Lazar MA, Brown M. Cofactor dynamics and sufficiency in estrogen receptor-regulated transcription. Cell 103: 843-852 (2000) https://doi.org/10.1016/S0092-8674(00)00188-4
  25. Gong J, Zhu J, Goodman OB Jr, Pestell RG, Schlegel PN, Nanus DM, Shen R. Activation of p300 histone acetyltransferase activity and acetylation of the androgen receptor by bombesin in prostate cancer cells. Oncogene 25: 2011-2021 (2006) https://doi.org/10.1038/sj.onc.1209231
  26. Kim KA, Chang HY, Choi SW, Yoon JW, Lee C. Cytotoxic effects of extracts from Tremella fuciformis strain FB001 on the human colon adenocarcinoma cell line DLD-1. Food Sci. Biotechnol. 15: 889-895 (2006)
  27. Hwang ES, Bowen P. Effect of lycopene on lipid peroxidation and oxidative DNA damage in LNCaP human prostate cancer cells. Food Sci. Biotechnol. 13: 297-301 (2004)
  28. Gregory CW, Hamil KG, Kim D, Hall SH, Pretlow TG, Mohler JL, French FS. Androgen receptor expression in androgen-independent prostate cancer is associated with increased expression of androgen-regulated genes. Cancer Res. 58: 5718-5724 (1998)
  29. Gaughan L, Logan IR, Neal DE, Robson CN. Regulation of androgen receptor and histone deacetylase 1 by Mdm2-mediated ubiquitylation. Nucleic Acids Res. 33: 13-26 (2005) https://doi.org/10.1093/nar/gki141
  30. Marshall TW, Link KA, Petre-Draviam CE, Knudsen KE. Differential requirement of SWI/SNF for androgen receptor activity. J. Biol. Chem. 278: 30605-30613 (2003) https://doi.org/10.1074/jbc.M304582200
  31. Korkmaz CG, Fronsdal K, Zhang Y, Lorenzo PI, Saatcioglu F. Potentiation of androgen receptor transcriptional activity by inhibition of histone deacetylatiori-rescue of transcriptionally compromised mutants. J. Endocrinol. 182: 377-389 (2004) https://doi.org/10.1677/joe.0.1820377