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01.08.2013 | PRECLINICAL STUDIES

Tetra-O-methyl nordihydroguaiaretic acid, an inhibitor of Sp1-mediated survivin transcription, induces apoptosis and acts synergistically with chemo-radiotherapy in glioblastoma cells

verfasst von: Angel Mauricio Castro-Gamero, Kleiton Silva Borges, Daniel Antunes Moreno, Veridiana Kill Suazo, Mayara Missono Fujinami, Rosane de Paula Gomes Queiroz, Harley Francisco de Oliveira, Carlos Gilberto Carlotti Jr., Carlos Alberto Scrideli, Luiz Gonzaga Tone

Erschienen in: Investigational New Drugs | Ausgabe 4/2013

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Summary

Glioblastoma (GBM), one of the most malignant human neoplasias, responds poorly to current treatment modalities, with temozolomide (TMZ) being the drug most frequently used for its treatment. Tetra-O-methyl Nordihydroguaiaretic Acid (M4N) is a global transcriptional repressor of genes dependent on the Sp1 transcription factor, such as Survivin and Cdk1. In the present study we evaluated the gene expression of Survivin, its spliced variants and Cdk1 in GBM samples and cell lines. Moreover, we investigated the effects of M4N combined or not with TMZ and/or radiation on GBM primary cultures and cell lines. qRT-PCR assays were performed to determine the Survivin-spliced variants and Cdk1 gene mRNA expression in GBM tumor samples and cell lines. Cell proliferation was measured by XTT assay and cell cycle and apoptosis were determined by flow cytometry. Drug combination analyses using different schedules of administration (simultaneous and sequential) were performed on GBM cell lines and primary cultures based on the Chou-Talalay method. For clonogenic survival, doses of 2, 4, and 6 Gy of gamma radiation. were used. All Survivin-spliced variants and the Cdk1 gene were expressed in GBM samples (n = 16) and cell lines (n = 6), except the Survivin-2B variant that was only expressed in GBM cell lines. M4N treatment down regulated the expression of Cdk1, Survivin and the Survivin-ΔEx3 variant, while the Survivin-2B variant was up-regulated. M4N decreased the cell proliferation separately and synergistically with TMZ, and enhanced the effects of radiation, mainly when associated with TMZ. M4N also induced apoptotic cell death, decreased the mitotic index and arrested the cell cycle mainly in the G2/M phase. Our results suggest a potential clinical application of M4N in combination with TMZ and radiation for GB treatment.

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Khasraw M, Lassman AB (2010) Advances in the treatment of malignant gliomas. Curr Oncol Rep 12:26–33. doi:10.1007/s11912-009-0077-4 PubMedCrossRef

Benítez JA, Domínguez-Monzón G, Segovia J (2008) Conventional and gene therapy strategies for the treatment of brain tumors. Curr Med Chem 15:729–742PubMedCrossRef

Henson JW (2006) Treatment of glioblastoma multiforme: a new standard. Arch Neurol 63:337–341PubMedCrossRef

Verheij M, Bartelink H (2000) Radiation-induced apoptosis. Cell Tissue Res 301:133–142. doi:10.1007/s004410000188 PubMedCrossRef

Shah MA, Schwartz GK (2001) Cell cycle-mediated drug resistance: an emerging concept in cancer therapy. Clin Cancer Res 7(8):2168–2181PubMed

Sah NK, Khan Z, Khan GJ, Bisen PS (2006) Structural, functional and therapeutic biology of survivin. Cancer Lett 244:164–171. doi:10.1016/j.canlet.2006.03.007 PubMedCrossRef

Ambrosini G, Adida C, Sirugo G, Altieri DC (1998) Induction of apoptosis and inhibition of cell proliferation by survivin gene targeting. J Biol Chem 273:11177–11182. doi:10.1074/jbc.273.18.11177 PubMedCrossRef

Altieri DC (2003) Survivin, versatile modulation of cell division and apoptosis in cancer. Oncogene 22:8581–8589. doi:10.1038/sj.onc.1207113 PubMedCrossRef

Ryan BM, O’Donovan N, Duffy MJ (2009) Survivin: a new target for anti-cancer therapy. Cancer Treat Rev 35:553–562. doi:10.1016/j.ctrv.2009.05.003 PubMedCrossRef

10.

Blanc-Brude OP, Mesri M, Wall NR, Plescia J, Dohi T, Altieri DC (2003) Therapeutic targeting of the survivin pathway in cancer: initiation of mitochondrial apoptosis and suppression of tumor-associated angiogenesis. Clin Cancer Res 9:2683–2692PubMed

11.

Chakravarti A, Noll E, Black PM, Finkelstein DF, Finkelstein DM, Dyson NJ, Loeffler JS (2002) Quantitatively determined survivin expression levels are of prognostic value in human gliomas. J Clin Oncol 20(4):1063–1068PubMedCrossRef

12.

Chakravarti A, Zhai GG, Zhang M, Malhotra R, Latham DE, Delaney MA, Robe P, Nestler U, Song Q, Loeffler J (2004) Survivin enhances radiation resistance in primary human glioblastoma cells via caspase-independent mechanisms. Oncogene 23:7494–7506. doi:10.1038/sj.onc.1208049 PubMedCrossRef

13.

Reichert S, Rödel C, Mirsch J, Harter PN, Tomicic MT, Mittelbronn M, Kaina B, Rödel F (2011) Survivin inhibition and DNA double-strand break repair: a molecular mechanism to overcome radioresistance in glioblastoma. Radiother Oncol 101(1):51–58. doi:10.1016/j.radonc.2011.06.037 PubMedCrossRef

14.

O’Connor DS, Grossman D, Plescia J, Li F, Zhang H, Villa A, Tognin S, Marchisio PC, Altieri DC (2000) Regulation of apoptosis at cell division by p34cdc2 phosphorylation of survivin. Proc Natl Acad Sci USA 97(24):13103–13107. doi:10.1073ypnas.240390697 PubMedCrossRef

15.

Wang Q, Su L, Liu N, Zhang L, Xu W, Fang H (2011) Cyclin dependent kinase 1 inhibitors: a review of recent progress. Curr Med Chem 18(13):2025–2043PubMedCrossRef

16.

Malumbres M, Barbacid M (2001) To cycle or not to cycle: a critical decision in cancer. Nat Rev Cancer 1:222–231PubMedCrossRef

17.

Malumbres M, Barbacid M (2009) Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer 9(3):153–166. doi:10.1038/nrc2602 PubMedCrossRef

18.

Bodey B, Siegel SE, Kaiser HE (2002) Expression of proline-directed protein kinase, (p34cdc2/p58cyclin A), a novel cell proliferation marker in childhood brain tumors. In Vivo 16:589–594PubMed

19.

Chen H, Huang Q, Dong J, Zhai DZ, Wang AD, Lan Q (2008) Overexpression of CDC2/CyclinB1 in gliomas, and CDC2 depletion inhibits proliferation of human glioma cells in vitro and in vivo. BMC Cancer 8:29. doi:10.1186/1471-2407-8-29 PubMedCrossRef

20.

Heller JD, Kuo J, Wu TC, Kast WM, Huang RC (2001) Tetra-O-methyl nordihydroguaiaretic acid induces G2 arrest in mammalian cells and exhibits tumoricidal activity in vivo. Cancer Res 61:5499–5504PubMed

21.

Chang CC, Heller JD, Kuo J, Huang RC (2004) Tetra-O-methyl nordihydroguaiaretic acid induces growth arrest and cellular apoptosis by inhibiting Cdc2 and survivin expression. Proc Natl Acad Sci U S A 101(36):13239–13244. doi:10.1073/pnas.0405407101 PubMedCrossRef

22.

Grossman SA, Ye X, Peereboom D, Rosenfeld MR, Mikkelsen T, Supko JG, Desideri S, Adult Brain Tumor Consortium (2012) Phase I study of terameprocol in patients with recurrent high-grade gliomas. Neuro-Oncology 14(4):511–517. doi:10.1093/neuonc/nor230 PubMedCrossRef

23.

Louis DN, Ohgaki H, Wiestler OD (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114:97–109. doi:10.1007/s00401-007-0243-4 PubMedCrossRef

24.

Borges KS, Castro-Gamero AM, Moreno DA, da Silva Silveira V, Brassesco MS, de Paula Queiroz RG, de Oliveira HF, Carlotti CG Jr, Scrideli CA, Tone LG (2012) Inhibition of Aurora kinases enhances chemosensitivity to temozolomide and causes radiosensitization in glioblastoma cells. J Cancer Res Clin Oncol 138(3):405–414. doi:10.1007/s00432-011-1111-0 PubMedCrossRef

25.

Brassesco MS, Valera ET, Neder L, Castro-Gamero AM, Arruda D, Machado HR, Sakamoto-Hojo ET, Tone LG (2009) Polyploidy in atypical choroid plexus papilloma of the posterior fossa. Neuropathology 29:293–298. doi:10.1111/j.1440-1789.2008.00949.x PubMedCrossRef

26.

Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(−delta delta C(T)) method. Methods 25(4):402–408. doi:10.1006/meth.2001.1262 PubMedCrossRef

27.

Valente V, Teixeira SA, Neder L, Okamoto OK, Oba-Shinjo SM, Marie SK, Scrideli CA, Paçó-Larson ML, Carlotti CG Jr (2009) Selection of suitable housekeeping genes for expression analysis in glioblastoma using quantitative RT-PCR. BMC Mol Biol 10:17. doi:10.1186/1471-2199-10-17 PubMedCrossRef

28.

Castro-Gamero AM, Borges KS, da Silva Silveira V, Lira RC, de Paula Gomes Queiroz R, Valera FC, Scrideli CA, Umezawa K, Tone LG (2012) Inhibition of nuclear factor-κB by dehydroxymethylepoxyquinomicin induces schedule-dependent chemosensitivity to anticancer drugs and enhances chemoinduced apoptosis in osteosarcoma cells. Anticancer Drugs 23(6):638–650. doi:10.1097/CAD.0b013e328350e835 PubMedCrossRef

29.

Chou TC, Talalay P (1984) Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzym Regul 22:27–55CrossRef

30.

Franken NA, Rodermond HM, Stap J, Haveman J, van Bree C (2006) Clonogenic assay of cells in vitro. Nat Protoc 1:2315–2319. doi:10.1038/nprot.2006.339 PubMedCrossRef

31.

Ohgaki H, Kleihues P (2007) Genetic pathways to primary and secondary glioblastoma. Am J Pathol 170:1445–1453. doi:10.2353/ajpath.2007.070011 PubMedCrossRef

32.

Shirahata M, Oba S, Iwao-Koizumi K, Saito S, Ueno N, Oda M, Hashimoto N, Ishii S, Takahashi JA, Kato K (2009) Using gene expression profiling to identify a prognostic molecular spectrum in gliomas. Cancer Sci 100:165–172. doi:10.1111/j.1349-7006.2008.01002.x PubMedCrossRef

33.

Perry J, Okamoto M, Guiou M, Shirai K, Errett A, Chakravarti A (2012) Novel therapies in glioblastoma. Neurol Res Int 2012:428–565. doi:10.1155/2012/428565

34.

Lackner MR, Wilson TR, Settleman J (2012) Mechanisms of acquired resistance to targeted cancer therapies. Future Oncol 8(8):999–1014. doi:10.2217/fon.12.86 PubMedCrossRef

35.

Altieri DC (2008) New wirings in the survivin networks. Oncogene 27:6276–6284. doi:10.1038/onc.2008.303 PubMedCrossRef

36.

Shapiro GI (2006) Cyclin-dependent kinase pathways as targets for cancer treatment. J Clin Oncol 24(11):1770–1783. doi:10.1200/JCO.2005.03.7689 PubMedCrossRef

37.

Yamada Y, Kuroiwa T, Nakagawa T, Kajimoto Y, Dohi T, Azuma H, Tsuji M, Kami K, Miyatake S (2003) Transcriptional expression of survivin and its splice variants in brain tumors in humans. J Neurosurg 99(4):738–745PubMedCrossRef

38.

Qian X, LaRochelle WJ, Ara G, Wu F, Petersen KD, Thougaard A, Sehested M, Lichenstein HS, Jeffers M (2006) Activity of PXD101, a histone deacetylase inhibitor, in preclinical ovarian cancer studies. Mol Cancer Ther 5:2086–2095PubMedCrossRef

39.

Lambert JD, Meyers RO, Timmermann BN, Dorr RT (2001) Tetra-O-methylnordihydroguaiaretic acid inhibits melanoma in vivo. Cancer Lett 171:47–56. doi:10.1016/S0304-3835(01)00560-2 PubMedCrossRef

40.

Meyers RO, Lambert JD, Hajicek N, Pourpak A, Kalaitzis JA, Dorr RT (2009) Synthesis, characterization, and anti-melanoma activity of tetra-O-substituted analogs of nordihydroguaiaretic acid. Bioorg Med Chem Lett 19:4752–4755. doi:10.1016/j.bmcl.2009.06.063 PubMedCrossRef

41.

Park R, Chang CC, Liang YC, Chung Y, Henry RA, Lin E, Mold DE, Huang RC (2005) Systemic treatment with tetra-O-methyl nordihydroguaiaretic acid suppresses the growth of human xenograft tumors. Clin Cancer Res 11:4601–4609. doi:10.1158/1078-0432.CCR-04-2188 PubMedCrossRef

42.

Mak DH, Schober WD, Chen W, Heller J, Andreeff M, Carter BZ (2007) Tetra-O-methyl nordihydroguaiaretic acid inhibits growth and induces death of leukemia cells independent of Cdc2 and survivin. Leuk Lymphoma 48:774–785. doi:10.1080/10428190601186143 PubMedCrossRef

43.

Zhu X, Ma Y, Liu D (2010) Novel agents and regimens for acute myeloid leukemia: 2009 ASH annual meeting highlights. J Hematol Oncol 3:17. doi:10.1186/1756-8722-3-17 PubMedCrossRef

44.

Hansel DE, Dhara S, Huang RC et al (2005) CDC2/CDK1 expression in esophageal adenocarcinoma and precursor lesions serves as a diagnostic and cancer progression marker and potential novel drug target. Am J Surg Pathol 29:390–399PubMedCrossRef

45.

Lopez RA, Goodman AB, Rhodes M, Blomberg JA, Heller J (2007) The anticancer activity of the transcription inhibitor terameprocol (meso-tetra-O-methyl nordihydroguaiaretic acid) formulated for systemic administration. Anticancer Drugs 18:933–939. doi:10.1097/CAD.0b013e32813148e0 PubMed

46.

Liu G, Yuan X, Zeng Z, Tunici P, Ng H, Abdulkadir IR, Lu L, Irvin D, Black KL, Yu JS (2006) Analysis of gene expression and chemoresistance of CD133+ cancer stem cells in glioblastoma. Mol Cancer 5:67. doi:10.1186/1476-4598-5-67 PubMedCrossRef

47.

Shah MA, Schwartz GK (2000) The relevance of drug sequence in combination chemotherapy. Drug Resist Updat 3(6):335–356. doi:10.1054/drup.2000.0165 PubMedCrossRef

48.

Hoffman WH, Biade S, Zilfou JT, Chen J, Murphy M (2002) Transcriptional repression of the antiapoptotic survivin gene by wild type p53. J Biol Chem 277(5):3247–3257. doi:10.1074/jbc.M106643200 PubMedCrossRef

49.

Yamamoto H, Ngan CY, Monden M (2008) Cancer cells survive with survivin. Cancer Sci 99(9):1709–1714. doi:10.1111/j.1349-7006.2008.00870.x PubMedCrossRef

50.

Ishii N, Maier D, Merlo A, Tada M, Sawamura Y, Diserens AC, Van Meir EG (1999) Frequent co-alterations of TP53, p16/CDKN2A, p14ARF, PTEN tumor suppressor genes in human glioma cell lines. Brain Pathol 9(3):469–479PubMedCrossRef

51.

Sun Y, Giacalone NJ, Lu B (2011) Terameprocol (tetra-O-methyl nordihydroguaiaretic acid), an inhibitor of Sp1-mediated survivin transcription, induces radiosensitization in non-small cell lung carcinoma. J Thorac Oncol 6(1):8–14. doi:10.1097/JTO.0b013e3181fa646a PubMedCrossRef

52.

Iwasa T, Okamoto I, Suzuki M et al (2008) Radiosensitizing effect of YM155, a novel small-molecule survivin suppressant, in non-small cell lung cancer cell lines. Clin Cancer Res 14:6496–6504. doi:10.1158/1078-0432.CCR-08-0468 PubMedCrossRef

53.

Cao C, Mu Y, Hallahan DE, Lu B (2004) XIAP and survivin as therapeutic targets for radiation sensitization in preclinical models of lung cancer. Oncogene 23:7047–7052. doi:10.1038/sj.onc.1207929 PubMedCrossRef

54.

Rödel F, Frey B, Leitmann W, Capalbo G, Weiss C, Rödel C (2008) Survivin antisense oligonucleotides effectively radiosensitize colorectal cancer cells in both tissue culture and murine xenograft models. Int J Radiat Oncol Biol Phys 71:247–255. doi:10.1016/j.ijrobp.2008.02.011 PubMedCrossRef

55.

Kami K, Doi R, Koizumi M, Toyoda E, Mori T, Ito D, Kawaguchi Y, Fujimoto K, Wada M, Miyatake S, Imamura M (2005) Downregulation of survivin by siRNA diminishes radioresistance of pancreatic cancer cells. Surgery 138:299–305. doi:10.1016/j.surg.2005.05.009 PubMedCrossRef

56.

Eisele G, Weller M (2011) Targeting apoptosis pathways in glioblastoma. Cancer Lett. doi:10.1016/j.canlet.2010.12.012 [Epub ahead of print]

57.

Sgorbissa A, Tomasella A, Potu H, Manini I, Brancolini C (2011) Type I IFNs signaling and apoptosis resistance in glioblastoma cells. Apoptosis 16(12):1229–1244. doi:10.1007/s10495-011-0639-4 PubMedCrossRef

58.

Gaspar N, Sharp SY, Eccles SA, Gowan S, Popov S, Jones C, Pearson A, Vassal G, Workman P (2010) Mechanistic evaluation of the novel HSP90 inhibitor NVP-AUY922 in adult and pediatric glioblastoma. Mol Cancer Ther 9(5):1219–1233. doi:10.1158/1535-7163.MCT-09-0683 PubMedCrossRef

59.

Valera ET, de Freitas Cortez MA, de Paula Queiroz RG, de Oliveira FM, Brassesco MS, Jabado N, Faury D, Bobola MS, Machado HR, Scrideli CA, Tone LG (2009) Pediatric glioblastoma cell line shows different patterns of expression of transmembrane ABC transporters after in vitro exposure to vinblastine. Childs Nerv Syst 25(1):39–45. doi:10.1007/s00381-008-0740-3 PubMedCrossRef

60.

Bax DA, Little SE, Gaspar N et al (2009) Molecular and phenotypic characterisation of paediatric gliomas cell lines as models for preclinical drug development. PLoS One 4(4):e5209. doi:10.1371/journal.pone.0005209 PubMedCrossRef

61.

Mahotka C, Wenzel M, Springer E, Gabbert HE, Gerharz CD (1999) Survivin-deltaEx3 and survivin-2B: two novel splice variants of the apoptosis inhibitor survivin with different antiapoptotic properties. Cancer Res 59(24):6097–6102PubMed

62.

Sampath J, Pelus LM (2007) Alternative splice variants of survivin as potential targets in cancer. Curr Drug Discov Technol 43:174–191CrossRef

63.

Wang HW, Sharp TV, Koumi A, Koentges G, Boshoff C (2002) Characterization of an anti-apoptotic glycoprotein encoded by Kaposi’s sarcoma-associated herpes virus which resembles a spliced variant of human survivin. EMBO J 21(11):2602–2615. doi:10.1093/emboj/21.11.2602 PubMedCrossRef

64.

Zhu N, Gu L, Findley HW, Li F, Zhou M (2004) An alternatively spliced survivin variant is positively regulated by p53 and sensitizes leukemia cells to chemotherapy. Oncogene 2345:7545–7551. doi:10.1038/sj.onc.1208038 CrossRef

65.

Ling X, Cheng Q, Black JD, Li F (2007) Forced expression of survivin-2B abrogates mitotic cells and induces mitochondria-dependent apoptosis by blockade of tubulin polymerization and modulation of Bcl-2, Bax, and survivin. J Biol Chem 282(37):27204–27214. doi:10.1074/jbc.M705161200 PubMedCrossRef

66.

Zheng WY, Kang YY, Li LF, Xu YX, Ma XY (2011) Levels of effectiveness of gene therapies targeting survivin and its splice variants in human breast cancer cells. Drug Discov Ther 5(6):293–298. doi:10.5582/ddt.2011.v5.6.293 PubMed

67.

Jacob NK, Cooley JV, Shirai K, Chakravarti A (2012) Survivin splice variants are not essential for mitotic progression or inhibition of apoptosis induced by doxorubicin and radiation. Onco Targets Ther 5:7–20. doi:10.2147/OTT.S28147 PubMedCrossRef

Titel: Tetra-O-methyl nordihydroguaiaretic acid, an inhibitor of Sp1-mediated survivin transcription, induces apoptosis and acts synergistically with chemo-radiotherapy in glioblastoma cells
verfasst von: Angel Mauricio Castro-Gamero
Kleiton Silva Borges
Daniel Antunes Moreno
Veridiana Kill Suazo
Mayara Missono Fujinami
Rosane de Paula Gomes Queiroz
Harley Francisco de Oliveira
Carlos Gilberto Carlotti Jr.
Carlos Alberto Scrideli
Luiz Gonzaga Tone
Publikationsdatum: 01.08.2013
Verlag: Springer US
Erschienen in: Investigational New Drugs / Ausgabe 4/2013
Print ISSN: 0167-6997
Elektronische ISSN: 1573-0646
DOI: https://doi.org/10.1007/s10637-012-9917-4

Springer Medizin

Tetra-O-methyl nordihydroguaiaretic acid, an inhibitor of Sp1-mediated survivin transcription, induces apoptosis and acts synergistically with chemo-radiotherapy in glioblastoma cells

Summary

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Springer Medizin

Summary

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