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Resveratrol Represses Pokemon Expression in Human Glioma Cells

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An Erratum to this article was published on 04 June 2015

Abstract

POK erythroid myeloid ontogenic factor (Pokemon), an important proto-oncoprotein, is a transcriptional repressor that regulates the expression of many genes and plays an important role in tumorigenesis. Resveratrol (RSV), a natural polyphenolic compound, has many beneficial biological effects on health. In this study, we investigated the role of Pokemon in RSV-induced biological effects and the effect of RSV on the expression of Pokemon in glioma cells. We found that overexpression of Pokemon decreased RSV-induced cell apoptosis, senescence, and anti-proliferative effects. Moreover, we showed that RSV could efficiently decrease the activity of the Pokemon promoter and the expression of Pokemon. Meanwhile, RSV also inhibited Sp1 DNA binding activity to the Pokemon promoter; whereas, it did not influence the expression and nuclear translocation of Sp1. In addition, we found that RSV could increase the recruitment of HDAC1, but decreased p300 to the Pokemon promoter. Taken together, all these results extended our understanding on the anti-cancer mechanism of RSV in glioma cells.

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References

  1. Tamiya T, Takao S, Ichikawa T, Chayama K, Date I (2006) Successful chemotherapy for congenital malignant gliomas: a report of two cases. Pediatr Neurosurg 42:240–244

    Article  PubMed  Google Scholar 

  2. Sathornsumetee S, Rich JN (2006) New approaches to primary brain tumor treatment. Anticancer Drugs 17:1003–1016

    Article  CAS  PubMed  Google Scholar 

  3. Gusman J, Malonne H, Atassi G (2001) A reappraisal of the potential chemopreventive and chemotherapeutic properties of resveratrol. Carcinogenesis 22:1111–1117

    Article  CAS  PubMed  Google Scholar 

  4. Joe AK, Liu H, Suzui M, Vural ME, Xiao D, Weinstein IB (2002) Resveratrol induces growth inhibition, S-phase arrest, apoptosis, and changes in biomarker expression in several human cancer cell lines. Clin Cancer Res 8:893–903

    CAS  PubMed  Google Scholar 

  5. Saiko P, Szakmary A, Jaeger W, Szekeres T (2008) Resveratrol and its analogs: defense against cancer, coronary disease and neurodegenerative maladies or just a fad? Mutat Res 658:68–94

    Article  CAS  PubMed  Google Scholar 

  6. Bhat KPL, Kosmeder JW, Pezzuto JM (2001) Biological effects of resveratrol. Antioxid Redox Signal 3:1041–1064

    Article  CAS  PubMed  Google Scholar 

  7. Virgili M, Contestabile A (2000) Partial neuroprotection of in vivo excitotoxic brain damage by chronic administration of the red wine antioxidant agent, trans-resveratrol in rats. Neurosci Lett 281:123–126

    Article  CAS  PubMed  Google Scholar 

  8. Bhat KP, Pezzuto JM (2002) Cancer chemopreventive activity of resveratrol. Ann N Y Acad Sci 957:210–229

    Article  CAS  PubMed  Google Scholar 

  9. Osman AM, Al-Harthi SE, Alarabi OM, Elshal MF, Ramadan WS, Alaama MN, Al-Kreathy HM, Damanhouri ZA, Osman OH (2013) Chemosensetizing and cardioprotective effects of resveratrol in doxorubicin- treated animals. Cancer Cell Int 13:52

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Jiang H, Shang X, Wu H, Huang G, Wang Y, Al-Holou S, Gautam SC, Chopp M (2010) Combination treatment with resveratrol and sulforaphane induces apoptosis in human U251 glioma cells. Neurochem Res 35:152–161

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Castino R, Pucer A, Veneroni R, Morani F, Peracchio C, Lah TT, Isidoro C (2011) Resveratrol reduces the invasive growth and promotes the acquisition of a long-lasting differentiated phenotype in human glioblastoma cells. J Agric Food Chem 59:4264–4272

    Article  CAS  PubMed  Google Scholar 

  12. Bass TM, Weinkove D, Houthoofd K, Gems D, Partridge L (2007) Effects of resveratrol on lifespan in Drosophila melanogaster and Caenorhabditis elegans. Mech Ageing Dev 128:546–552

    Article  CAS  PubMed  Google Scholar 

  13. Valenzano DR, Terzibasi E, Genade T, Cattaneo A, Domenici L, Cellerino A (2006) Resveratrol prolongs lifespan and retards the onset of age-related markers in a short-lived vertebrate. Curr Biol 16:296–300

    Article  CAS  PubMed  Google Scholar 

  14. Morrison DJ, Pendergrast PS, Stavropoulos P, Colmenares SU, Kobayashi R, Hernandez N (1999) FBI-1, a factor that binds to the HIV-1 inducer of short transcripts (IST), is a POZ domain protein. Nucleic Acids Res 27:1251–1262

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Lee DK, Suh D, Edenberg HJ, Hur MW (2002) POZ domain transcription factor, FBI-1, repress transcription of ADH5/FDH by interacting with the zinc finger and interfering with DNA binding activity of SP1. J Biol Chem 277:26761–26768

    Article  CAS  PubMed  Google Scholar 

  16. Lee DK, Kang JE, Park HJ, Kim MH, Yim TH, Kim JM, Heo MK, Kim KY, Kwon HJ, Hur MW (2005) FBI-1 enhances transcription of the nuclear factor-kappaB (NF-kappaB)-responsive E-selectin gene by nuclear localization of the p65 subunit of NF-kappaB. J Biol Chem 280:27783–27791

    Article  CAS  PubMed  Google Scholar 

  17. Maeda T, Hobbs RM, Merghoub T, Guernah I, Zelent A, Cordon-Cardo C, Teruya-Feldstein J, Pandolfi PP (2005) Role of the proto-oncogene Pokemon in cellular transformation and ARF repression. Nature 433:278–285

    Article  CAS  PubMed  Google Scholar 

  18. Zhao ZH, Wang SF, Yu L, Wang J, Chang H, Yan WL, Zhang J, Fu K (2008) Overexpression of Pokemonin non-small cell lung cancer and foreshowing tumor biological behavior as well as clinical results. Lung Cancer 62:113–119

    Article  PubMed  Google Scholar 

  19. Aggarwal A, Hunter WJ 3rd, Aggarwal H, Silva ED, Davey MS, Murphy RF, Agrawal DK (2010) Expression of leukemia/lymphoma-related factor (LRF/POKEMON) in human breast carcinoma and other cancers. Exp Mol Pathol 89:140–148

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Aggarwal H, Aggarwal A, Hunter WJ 3rd, Yohannes P, Khan AU, Agrawal DK (2011) Expression of leukemia/lymphoma related factor (LRF/Pokemon) in human benign prostate hyperplasia and prostate cancer. Exp Mol Pathol 90:226–230

    Article  CAS  PubMed  Google Scholar 

  21. Fang F, Yang L, Tao Y, Qin W (2012) FBI-1 promotes cell proliferation and enhances resistance to chemotherapy of hepatocellular carcinoma in vitro and in vivo. Cancer 118:134–146

    Article  CAS  PubMed  Google Scholar 

  22. Maeda T, Hobbs RM, Pandolfi PP (2005) The transcription factor Pokemon: a new key player in cancer pathogenesis. Cancer Res 65:8575–8578

    Article  CAS  PubMed  Google Scholar 

  23. Notas G, Nifli AP, Kampa M, Vercauteren J, Kouroumalis E, Castanas E (2006) Resveratrol exerts its antiproliferative effect on HepG2 hepatocellular carcinoma cells, by inducing cell cycle arrest, and NOS activation. Biochim Biophys Acta 1760:1657–1666

    Article  CAS  PubMed  Google Scholar 

  24. Can G, Cakir Z, Kartal M, Gunduz U, Baran Y (2012) Apoptotic effects of resveratrol, a grape polyphenol, on imatinib-sensitive and resistant K562 chronic myeloid leukemia cells. Anticancer Res 32:2673–2678

    CAS  PubMed  Google Scholar 

  25. Cui J, Sun RH, Yu YP, Gou SM, Zhao G, Wang CY (2010) Antiproliferative effect of resveratrol in pancreatic cancer cells. Phytother Res 24:1637–1644

    Article  CAS  PubMed  Google Scholar 

  26. Yang YT, Zhou XW, Zhu X, Zhang CF, Yang ZX, Xu L, Huang PT (2008) Cloning and functional analysis of 5′-upstream region of the Pokemon gene. FEBS J 275:1860–1873

    Article  CAS  PubMed  Google Scholar 

  27. Yang YT, Yu YL, Yang GD, Zhang JD, Zheng CC (2009) Tissue specific expression of the PNZIP promoter is mediated by combinatorial of different cis-elements and a novel transcriptional factor. Nucleic Acids Res 37:2630–2644

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Rovin RA, Winn R (2005) Pokemon expression in malignant glioma: an application of bioinformatics methods. Neurosurg Focus 19:E8

    Article  PubMed  Google Scholar 

  29. Zhu X, Dai Y, Chen Z, Xie J, Zeng W, Lin Y (2013) Knockdown of Pokemon protein expression inhibits hepatocellular carcinoma cell proliferation by suppression of AKT activity. Oncol Res 20:377–281

    Article  CAS  PubMed  Google Scholar 

  30. Li YN, Xu SX, Wang XW, Shi H, Sun ZL, Yang Z (2013) Tumor-specific RNA interference targeting Pokemon suppresses tumor growth and induces apoptosis in prostate cancer. Urology 81:467.e1–e7

    Google Scholar 

  31. Choi WI, Jeon BN, Yun CO, Kim PH, Kim SE, Choi KY, Kim SH, Hur MW (2009) Proto-oncogene FBI-1 represses transcription of p21CIP1 by inhibition of transcription activation by p53 and Sp1. J Biol Chem 284:12633–12644

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Jeon BN, Yoo JY, Choi WI, Lee CE, Yoon HG, Hur MW (2008) Proto-oncogene FBI-1 (Pokemon/ZBTB7A) represses transcription of the tumor suppressor Rb gene via binding competition with Sp1 and recruitment of co-repressors. J Biol Chem 283:33199–33210

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  33. Filippi-Chiela EC, Thomé MP, Bueno e Silva MM, Pelegrini AL, Ledur PF, Garicochea B, Zamin LL, Lenz G (2013) Resveratrol abrogates the temozolomide-induced G2 arrest leading to mitotic catastrophe and reinforces the temozolomide-induced senescence in glioma cells. BMC Cancer 13:147

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Yuan Y, Xue X, Guo RB, Sun XL, Hu G (2012) Resveratrol enhances the antitumor effects of temozolomide in glioblastoma via ROS-dependent AMPK-TSC-mTOR signaling pathway. CNS Neurosci Ther 18:536–546

    Article  CAS  PubMed  Google Scholar 

  35. Hung JJ, Wang YT, Chang WC (2006) Sp1 deacetylation induced by phorbol ester recruits p300 to activate 12(S)-lipoxygenase gene transcription. Mol Cell Biol 26:1770–1785

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. Cui JJ, Yang YT, Zhang CF, Hu PL, Bai XH, Liu XL, Song HB (2011) FBI-1 functions as a novel AR co-repressor in prostate cancer cells. Cell Mol Life Sci 68:1091–1103

  37. Aggarwal BB, Bhardwaj A, Aggarwal RS, Seeram NP, Shishodia S, Takada Y (2004) Role of resveratrol in prevention and therapy of cancer: preclinical and clinical studies. Anticancer Res 24:2783–2840

    CAS  PubMed  Google Scholar 

  38. Shi Q, Le X, Abbruzzese JL, Peng Z, Qian CN, Tang H, Xiong Q, Wang B, Li XC, Xie K (2001) Constitutive Sp1 activity is essential for differential constitutive expression of vascular endothelial growth factor in human pancreatic adenocarcinoma. Cancer Res 61:4143–4154

    CAS  PubMed  Google Scholar 

  39. Yao JC, Wang L, Wei D, Gong W, Hassan M, Wu TT, Mansfield P, Ajani J, Xie K (2004) Association between expression of transcription factor Sp1 and increased vascular endothelial growth factor expression, advanced stage, and poor survival in patients with resected gastric cancer. Clin Cancer Res 10:4109–4117

    Article  CAS  PubMed  Google Scholar 

  40. Guan H, Cai J, Zhang N, Wu J, Yuan J, Li J, Li M (2012) Sp1 is upregulated in human glioma, promotes MMP-2-mediated cell invasion and predicts poor clinical outcome. Int J Cancer 130:593–601

    Article  CAS  PubMed  Google Scholar 

  41. Kim YA, Lim SY, Rhee SH, Park KY, Kim CH, Choi BT, Lee SJ, Park YM, Choi YH (2006) Resveratrol inhibits inducible nitric oxide synthase and cyclooxygenase-2 expression in beta-amyloid-treated C6 glioma cells. Int J Mol Med 17:1069–1075

    CAS  PubMed  Google Scholar 

  42. Kim AL, Zhu Y, Zhu H, Han L, Kopelovich L, Bickers DR, Athar M (2006) Resveratrol inhibits proliferation of human epidermoid carcinoma A431 cells by modulating MEK1 and AP-1 signalling pathways. Exp Dermatol 15:53–46

    Google Scholar 

  43. Yeh CB, Hsieh MJ, Lin CW, Chiou HL, Lin PY, Chen TY, Yang SF (2013) The antimetastatic effects of resveratrol on hepatocellular carcinoma through the downregulation of a metastasis-associated protease by SP-1 modulation. PLoS ONE 8:e56661

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  44. Ren F, Zhang S, Mitchell SH, Butler R, Young CY (2000) Tea polyphenols down-regulate the expression of the androgen receptor in LNCaP prostate cancer cells. Oncogene 19:1924–1932

    Article  CAS  PubMed  Google Scholar 

  45. Hsu TI, Wang MC, Chen SY, Huang ST, Yeh YM, Su WC, Chang WC, Hung JJ (2012) Betulinic acid decreases specificity protein 1 (Sp1) level via increasing the sumoylation of sp1 to inhibit lung cancer growth. Mol Pharmacol 82:1115–1128

    Article  CAS  PubMed  Google Scholar 

  46. Bouwman P, Philipsen S (2002) Regulation of the activity of Sp1-related transcription factors. Mol Cell Endocrinol 195:27–38

    Article  CAS  PubMed  Google Scholar 

  47. Kamemura K, Hart GW (2003) Dynamic interplay between O-glycosylation and O-phosphorylation of nucleocytoplasmic proteins: a new paradigm for metabolic control of signal transduction and transcription. Prog Nucleic Acid Res Mol Biol 73:107–136

    Article  CAS  PubMed  Google Scholar 

  48. Zhao S, Venkatasubbarao K, Li S, Freeman JW (2003) Requirement of a specific Sp1 site for histone deacetylase-mediated repression of transforming growth factor β type II receptor expression in human pancreatic cancer cells. Cancer Res 63:2624–2630

    CAS  PubMed  Google Scholar 

  49. Waby JS, Chirakkal H, Yu C, Griffiths GJ, Benson RS, Bingle CD, Corfe BM (2010) Sp1 acetylation is associated with loss of DNA binding at promoters associated with cell cycle arrest and cell death in a colon cell line. Mol Cancer 9:275

    Article  PubMed Central  PubMed  Google Scholar 

  50. Glass CK, Rosenfeld MG (2000) The coregulator exchange in transcriptional functions of nuclear receptors. Genes Dev 14:121–141

    CAS  PubMed  Google Scholar 

  51. Suzuki T, Kimura A, Nagai R, Horikoshi M (2000) Regulation of interaction of the acetyltransferase region of p300 and the DNA-binding domain of Sp1 on and through DNA binding. Genes Cells 5:29–41

    Article  CAS  PubMed  Google Scholar 

  52. Billon N, Carlisi D, Datto MB, van Grunsven LA, Watt A, Wang XF, Rudkin BB (1999) Cooperation of Sp1 and p300 in the induction of the CDK inhibitor p21WAF1/CIP1 during NGF-mediated neuronal differentiation. Oncogene 18:2872–2882

    Article  CAS  PubMed  Google Scholar 

  53. Varshochi R, Halim F, Sunters A, Alao JP, Madureira PA, Hart SM, Ali S, Vigushin DM, Coombes RC, Lam EW (2005) ICI182,780 induces p21Waf1 gene transcription through releasing histone deacetylase 1 and estrogen receptor alpha from Sp1 sites to induce cell cycle arrest in MCF-7 breast cancer cell line. J Biol Chem 280:3185–3196

    Article  CAS  PubMed  Google Scholar 

  54. Kang JE, Kim MH, Lee JA, Park H, Min-Nyung L, Auh CK, Hur MW (2005) Histone deacetylase-1 represses transcription by interacting with zinc-fingers and interfering with the DNA binding activity of Sp1. Cell Physiol Biochem 16:23–30

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the grant from the National Natural Science Foundation of China (31271154, 31171032),National Basic Research Program (2010CB912003), the Development Project of Science and Technology sponsored by Beijing Education Committee (KM201310025001), and the Specialized Research Fund for the Doctoral Program of Higher Education (20111107120011).

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Correspondence to Yutao Yang or Zhi-Qing David Xu.

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Yang, Y., Cui, J., Xue, F. et al. Resveratrol Represses Pokemon Expression in Human Glioma Cells. Mol Neurobiol 53, 1266–1278 (2016). https://doi.org/10.1007/s12035-014-9081-2

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