Skip to main content
Top
Published in: Journal of Neuro-Oncology 1/2012

01-01-2012 | Laboratory Investigation - Human/Animal Tissue

Norcantharidin impairs medulloblastoma growth by inhibition of Wnt/β-catenin signaling

Authors: Flora Cimmino, Maria Nunzia Scoppettuolo, Marianeve Carotenuto, Pasqualino De Antonellis, Valeria Di Dato, Gennaro De Vita, Massimo Zollo

Published in: Journal of Neuro-Oncology | Issue 1/2012

Login to get access

Abstract

Medulloblastoma is one of the leading causes of morbidity and mortality in pediatric cancer. Wnt-active tumors, an independent molecular subgroup in medulloblastoma, are characterized by a distinct pattern of genomic aberrations. We assessed the anticancer activity of cantharidin and norcantharidin against medulloblastoma, as cell lines in vitro and in athymic nude mice in vivo. Cantharidin and norcantharidin treatment impaired the growth of DAOY and UW228 medulloblastoma cells and promoted the loss of β-catenin activation and the β-catenin nuclearization linked to N-cadherin impairment in vitro. Intra-peritoneal administration of norcantharidin inhibited the growth of intra-cerebellum tumors in orthotopic xenograft nude mice. Analysis of the xenograft tissues revealed enhanced neuronal differentiation and reduced β-catenin expression. Our findings suggest that norcantharidin has potential therapeutic applications in the treatment of medulloblastoma as a result of its ability to cross the blood–brain barrier and its impairment of Wnt-β-catenin signaling.
Appendix
Available only for authorised users
Literature
1.
go back to reference de Bont JM, Packer RJ, Michiels EM, den Boer ML, Pieters R (2008) Biological background of pediatric medulloblastoma and ependymoma: a review from a translational research perspective. Neuro Oncol 10(6):1040–1060PubMedCrossRef de Bont JM, Packer RJ, Michiels EM, den Boer ML, Pieters R (2008) Biological background of pediatric medulloblastoma and ependymoma: a review from a translational research perspective. Neuro Oncol 10(6):1040–1060PubMedCrossRef
2.
go back to reference Wang Q, Li H, Liu N, Chen XY, Wu ML, Zhang KL, Kong QY, Liu J (2008) Correlative analyses of notch signaling with resveratrol-induced differentiation and apoptosis of human medulloblastoma cells. Neurosci Lett 438(2):168–173PubMedCrossRef Wang Q, Li H, Liu N, Chen XY, Wu ML, Zhang KL, Kong QY, Liu J (2008) Correlative analyses of notch signaling with resveratrol-induced differentiation and apoptosis of human medulloblastoma cells. Neurosci Lett 438(2):168–173PubMedCrossRef
3.
go back to reference Yang ZJ, Ellis T, Markant SL, Read TA, Kessler JD, Bourboulas M, Schuller U, Machold R, Fishell G, Rowitch DH, Wainwright BJ, Wechsler-Reya RJ (2008) Medulloblastoma can be initiated by deletion of patched in lineage-restricted progenitors or stem cells. Cancer Cell 14(2):135–145PubMedCrossRef Yang ZJ, Ellis T, Markant SL, Read TA, Kessler JD, Bourboulas M, Schuller U, Machold R, Fishell G, Rowitch DH, Wainwright BJ, Wechsler-Reya RJ (2008) Medulloblastoma can be initiated by deletion of patched in lineage-restricted progenitors or stem cells. Cancer Cell 14(2):135–145PubMedCrossRef
4.
go back to reference Gilbertson RJ, Ellison DW (2008) The origins of medulloblastoma subtypes. Annu Rev Pathol 3:341–365PubMedCrossRef Gilbertson RJ, Ellison DW (2008) The origins of medulloblastoma subtypes. Annu Rev Pathol 3:341–365PubMedCrossRef
5.
go back to reference Guessous F, Li Y, Abounader R (2008) Signaling pathways in medulloblastoma. J Cell Physiol 217(3):577–583PubMedCrossRef Guessous F, Li Y, Abounader R (2008) Signaling pathways in medulloblastoma. J Cell Physiol 217(3):577–583PubMedCrossRef
6.
go back to reference Grotzer MA, von Hoff K, von Bueren AO, Shalaby T, Hartmann W, Warmuth-Metz M, Emser A, Kortmann RD, Kuehl J, Pietsch T, Rutkowski S (2007) Which clinical and biological tumor markers proved predictive in the prospective multicenter trial HIT’91—implications for investigating childhood medulloblastoma. Klin Padiatr 219(6):312–317PubMedCrossRef Grotzer MA, von Hoff K, von Bueren AO, Shalaby T, Hartmann W, Warmuth-Metz M, Emser A, Kortmann RD, Kuehl J, Pietsch T, Rutkowski S (2007) Which clinical and biological tumor markers proved predictive in the prospective multicenter trial HIT’91—implications for investigating childhood medulloblastoma. Klin Padiatr 219(6):312–317PubMedCrossRef
7.
go back to reference Pfister S, Remke M, Benner A, Mendrzyk F, Toedt G, Felsberg J, Wittmann A, Devens F, Gerber NU, Joos S, Kulozik A, Reifenberger G, Rutkowski S, Wiestler OD, Radlwimmer B, Scheurlen W, Lichter P, Korshunov A (2009) Outcome prediction in pediatric medulloblastoma based on DNA copy-number aberrations of chromosomes 6q and 17q and the MYC and MYCN loci. J Clin Oncol 27(10):1627–1636PubMedCrossRef Pfister S, Remke M, Benner A, Mendrzyk F, Toedt G, Felsberg J, Wittmann A, Devens F, Gerber NU, Joos S, Kulozik A, Reifenberger G, Rutkowski S, Wiestler OD, Radlwimmer B, Scheurlen W, Lichter P, Korshunov A (2009) Outcome prediction in pediatric medulloblastoma based on DNA copy-number aberrations of chromosomes 6q and 17q and the MYC and MYCN loci. J Clin Oncol 27(10):1627–1636PubMedCrossRef
8.
go back to reference Ellison DW, Kocak M, Dalton J, Megahed H, Lusher ME, Ryan SL, Zhao W, Nicholson SL, Taylor RE, Bailey S, Clifford SC (2010) Definition of disease-risk stratification groups in childhood medulloblastoma using combined clinical, pathologic, and molecular variables. J Clin Oncol 29:1400–1407PubMedCrossRef Ellison DW, Kocak M, Dalton J, Megahed H, Lusher ME, Ryan SL, Zhao W, Nicholson SL, Taylor RE, Bailey S, Clifford SC (2010) Definition of disease-risk stratification groups in childhood medulloblastoma using combined clinical, pathologic, and molecular variables. J Clin Oncol 29:1400–1407PubMedCrossRef
9.
go back to reference Clifford SC, O’Toole K, Ellison DW (2009) Chromosome 1q gain is not associated with a poor outcome in childhood medulloblastoma: requirements for the validation of potential prognostic biomarkers. Cell Cycle 8(5):787PubMedCrossRef Clifford SC, O’Toole K, Ellison DW (2009) Chromosome 1q gain is not associated with a poor outcome in childhood medulloblastoma: requirements for the validation of potential prognostic biomarkers. Cell Cycle 8(5):787PubMedCrossRef
10.
go back to reference Kool M, Koster J, Bunt J, Hasselt NE, Lakeman A, van Sluis P, Troost D, Meeteren NS, Caron HN, Cloos J, Mrsic A, Ylstra B, Grajkowska W, Hartmann W, Pietsch T, Ellison D, Clifford SC, Versteeg R (2008) Integrated genomics identifies five medulloblastoma subtypes with distinct genetic profiles, pathway signatures and clinicopathological features. PLoS One 3(8):e3088PubMedCrossRef Kool M, Koster J, Bunt J, Hasselt NE, Lakeman A, van Sluis P, Troost D, Meeteren NS, Caron HN, Cloos J, Mrsic A, Ylstra B, Grajkowska W, Hartmann W, Pietsch T, Ellison D, Clifford SC, Versteeg R (2008) Integrated genomics identifies five medulloblastoma subtypes with distinct genetic profiles, pathway signatures and clinicopathological features. PLoS One 3(8):e3088PubMedCrossRef
11.
go back to reference Northcott PA, Korshunov A, Witt H, Hielscher T, Eberhart CG, Mack S, Bouffet E, Clifford SC, Hawkins CE, French P, Rutka JT, Pfister S, Taylor MD (2010) Medulloblastoma comprises four distinct molecular variants. J Clin Oncol 29(11):1408–1414PubMedCrossRef Northcott PA, Korshunov A, Witt H, Hielscher T, Eberhart CG, Mack S, Bouffet E, Clifford SC, Hawkins CE, French P, Rutka JT, Pfister S, Taylor MD (2010) Medulloblastoma comprises four distinct molecular variants. J Clin Oncol 29(11):1408–1414PubMedCrossRef
12.
go back to reference Holthouse DJ, Dallas PB, Ford J, Fabian V, Murch AR, Watson M, Wong G, Bertram C, Egli S, Baker DL, Kees UR (2009) Classic and desmoplastic medulloblastoma: complete case reports and characterizations of two new cell lines. Neuropathology 29(4):398–409PubMedCrossRef Holthouse DJ, Dallas PB, Ford J, Fabian V, Murch AR, Watson M, Wong G, Bertram C, Egli S, Baker DL, Kees UR (2009) Classic and desmoplastic medulloblastoma: complete case reports and characterizations of two new cell lines. Neuropathology 29(4):398–409PubMedCrossRef
13.
go back to reference Katoh Y, Katoh M (2009) Hedgehog target genes: mechanisms of carcinogenesis induced by aberrant hedgehog signaling activation. Curr mol med 9(7):873–886PubMedCrossRef Katoh Y, Katoh M (2009) Hedgehog target genes: mechanisms of carcinogenesis induced by aberrant hedgehog signaling activation. Curr mol med 9(7):873–886PubMedCrossRef
14.
go back to reference Perez-Martinez A, Lassaletta A, Gonzalez-Vicent M, Sevilla J, Diaz MA, Madero L (2005) High-dose chemotherapy with autologous stem cell rescue for children with high risk and recurrent medulloblastoma and supratentorial primitive neuroectodermal tumors. J Neurooncol 71(1):33–38PubMedCrossRef Perez-Martinez A, Lassaletta A, Gonzalez-Vicent M, Sevilla J, Diaz MA, Madero L (2005) High-dose chemotherapy with autologous stem cell rescue for children with high risk and recurrent medulloblastoma and supratentorial primitive neuroectodermal tumors. J Neurooncol 71(1):33–38PubMedCrossRef
15.
go back to reference Rogers HA, Miller S, Lowe J, Brundler MA, Coyle B, Grundy RG (2009) An investigation of WNT pathway activation and association with survival in central nervous system primitive neuroectodermal tumours (CNS PNET). Br J Cancer 100(8):1292–1302PubMedCrossRef Rogers HA, Miller S, Lowe J, Brundler MA, Coyle B, Grundy RG (2009) An investigation of WNT pathway activation and association with survival in central nervous system primitive neuroectodermal tumours (CNS PNET). Br J Cancer 100(8):1292–1302PubMedCrossRef
16.
go back to reference Ellison DW, Onilude OE, Lindsey JC, Lusher ME, Weston CL, Taylor RE, Pearson AD, Clifford SC (2005) Beta-catenin status predicts a favorable outcome in childhood medulloblastoma: the United Kingdom children’s cancer study group brain tumour committee. J Clin Oncol 23(31):7951–7957PubMedCrossRef Ellison DW, Onilude OE, Lindsey JC, Lusher ME, Weston CL, Taylor RE, Pearson AD, Clifford SC (2005) Beta-catenin status predicts a favorable outcome in childhood medulloblastoma: the United Kingdom children’s cancer study group brain tumour committee. J Clin Oncol 23(31):7951–7957PubMedCrossRef
17.
go back to reference Rogers L, Pattisapu J, Smith RR, Parker P (1988) Medulloblastoma in association with the Coffin-Siris syndrome. Childs Nerv Syst 4(1):41–44PubMed Rogers L, Pattisapu J, Smith RR, Parker P (1988) Medulloblastoma in association with the Coffin-Siris syndrome. Childs Nerv Syst 4(1):41–44PubMed
18.
go back to reference Zhai Y, Wu R, Schwartz DR, Darrah D, Reed H, Kolligs FT, Nieman MT, Fearon ER, Cho KR (2002) Role of beta-catenin/T-cell factor-regulated genes in ovarian endometrioid adenocarcinomas. Am J Pathol 160(4):1229–1238PubMedCrossRef Zhai Y, Wu R, Schwartz DR, Darrah D, Reed H, Kolligs FT, Nieman MT, Fearon ER, Cho KR (2002) Role of beta-catenin/T-cell factor-regulated genes in ovarian endometrioid adenocarcinomas. Am J Pathol 160(4):1229–1238PubMedCrossRef
19.
go back to reference Efferth T, Rauh R, Kahl S, Tomicic M, Bochzelt H, Tome ME, Briehl MM, Bauer R, Kaina B (2005) Molecular modes of action of cantharidin in tumor cells. Biochem Pharmacol 69(5):811–818PubMedCrossRef Efferth T, Rauh R, Kahl S, Tomicic M, Bochzelt H, Tome ME, Briehl MM, Bauer R, Kaina B (2005) Molecular modes of action of cantharidin in tumor cells. Biochem Pharmacol 69(5):811–818PubMedCrossRef
20.
go back to reference Rauh R, Kahl S, Boechzelt H, Bauer R, Kaina B, Efferth T (2007) Molecular biology of cantharidin in cancer cells. Chin Med 2:8PubMedCrossRef Rauh R, Kahl S, Boechzelt H, Bauer R, Kaina B, Efferth T (2007) Molecular biology of cantharidin in cancer cells. Chin Med 2:8PubMedCrossRef
21.
go back to reference Shan HB, Cai YC, Liu Y, Zeng WN, Chen HX, Fan BT, Liu XH, Xu ZL, Wang B, Xian LJ (2006) Cytotoxicity of cantharidin analogues targeting protein phosphatase 2A. Anticancer Drugs 17(8):905–911PubMedCrossRef Shan HB, Cai YC, Liu Y, Zeng WN, Chen HX, Fan BT, Liu XH, Xu ZL, Wang B, Xian LJ (2006) Cytotoxicity of cantharidin analogues targeting protein phosphatase 2A. Anticancer Drugs 17(8):905–911PubMedCrossRef
22.
go back to reference Huan SK, Lee HH, Liu DZ, Wu CC, Wang CC (2006) Cantharidin-induced cytotoxicity and cyclooxygenase 2 expression in human bladder carcinoma cell line. Toxicology 223(1–2):136–143PubMedCrossRef Huan SK, Lee HH, Liu DZ, Wu CC, Wang CC (2006) Cantharidin-induced cytotoxicity and cyclooxygenase 2 expression in human bladder carcinoma cell line. Toxicology 223(1–2):136–143PubMedCrossRef
23.
go back to reference Dorn DC, Kou CA, Png KJ, Moore MA (2009) The effect of cantharidins on leukemic stem cells. Int J Cancer 124(9):2186–2199PubMedCrossRef Dorn DC, Kou CA, Png KJ, Moore MA (2009) The effect of cantharidins on leukemic stem cells. Int J Cancer 124(9):2186–2199PubMedCrossRef
24.
go back to reference Sagawa M, Nakazato T, Uchida H, Ikeda Y, Kizaki M (2008) Cantharidin induces apoptosis of human multiple myeloma cells via inhibition of the JAK/STAT pathway. Cancer Sci 99(9):1820–1826PubMedCrossRef Sagawa M, Nakazato T, Uchida H, Ikeda Y, Kizaki M (2008) Cantharidin induces apoptosis of human multiple myeloma cells via inhibition of the JAK/STAT pathway. Cancer Sci 99(9):1820–1826PubMedCrossRef
25.
go back to reference Hill TA, Stewart SG, Sauer B, Gilbert J, Ackland SP, Sakoff JA, McCluskey A (2007) Heterocyclic substituted cantharidin and norcantharidin analogues—synthesis, protein phosphatase (1 and 2A) inhibition, and anti-cancer activity. Bioorg Med Chem Lett 17(12):3392–3397PubMedCrossRef Hill TA, Stewart SG, Sauer B, Gilbert J, Ackland SP, Sakoff JA, McCluskey A (2007) Heterocyclic substituted cantharidin and norcantharidin analogues—synthesis, protein phosphatase (1 and 2A) inhibition, and anti-cancer activity. Bioorg Med Chem Lett 17(12):3392–3397PubMedCrossRef
26.
go back to reference Hill TA, Stewart SG, Gordon CP, Ackland SP, Gilbert J, Sauer B, Sakoff JA, McCluskey A (2008) Norcantharidin analogues: synthesis, anticancer activity and protein phosphatase 1 and 2A inhibition. Chem Med Chem 3(12):1878–1892PubMed Hill TA, Stewart SG, Gordon CP, Ackland SP, Gilbert J, Sauer B, Sakoff JA, McCluskey A (2008) Norcantharidin analogues: synthesis, anticancer activity and protein phosphatase 1 and 2A inhibition. Chem Med Chem 3(12):1878–1892PubMed
27.
go back to reference McCluskey A, Ackland SP, Bowyer MC, Baldwin ML, Garner J, Walkom CC, Sakoff JA (2003) Cantharidin analogues: synthesis and evaluation of growth inhibition in a panel of selected tumour cell lines. Bioorg Chem 31(1):68–79PubMedCrossRef McCluskey A, Ackland SP, Bowyer MC, Baldwin ML, Garner J, Walkom CC, Sakoff JA (2003) Cantharidin analogues: synthesis and evaluation of growth inhibition in a panel of selected tumour cell lines. Bioorg Chem 31(1):68–79PubMedCrossRef
28.
go back to reference Huang Y, Liu Q, Liu K, Yagasaki K, Zhang G (2009) Suppression of growth of highly-metastatic human breast cancer cells by norcantharidin and its mechanisms of action. Cytotechnology 59(3):209PubMedCrossRef Huang Y, Liu Q, Liu K, Yagasaki K, Zhang G (2009) Suppression of growth of highly-metastatic human breast cancer cells by norcantharidin and its mechanisms of action. Cytotechnology 59(3):209PubMedCrossRef
29.
go back to reference Luan J, Duan H, Liu Q, Yagasaki K, Zhang G (2010) Inhibitory effects of norcantharidin against human lung cancer cell growth and migration. Cytotechnology 62(4):349–355PubMedCrossRef Luan J, Duan H, Liu Q, Yagasaki K, Zhang G (2010) Inhibitory effects of norcantharidin against human lung cancer cell growth and migration. Cytotechnology 62(4):349–355PubMedCrossRef
30.
go back to reference Chen YJ, Tsai YM, Kuo CD, Ku KL, Shie HS, Liao HF (2009) Norcantharidin is a small-molecule synthetic compound with anti-angiogenesis effect. Life Sci 85(17–18):642–651PubMedCrossRef Chen YJ, Tsai YM, Kuo CD, Ku KL, Shie HS, Liao HF (2009) Norcantharidin is a small-molecule synthetic compound with anti-angiogenesis effect. Life Sci 85(17–18):642–651PubMedCrossRef
31.
go back to reference Chen YN, Chen JC, Yin SC, Wang GS, Tsauer W, Hsu SF, Hsu SL (2002) Effector mechanisms of norcantharidin-induced mitotic arrest and apoptosis in human hepatoma cells. Int J Cancer 100(2):158–165PubMedCrossRef Chen YN, Chen JC, Yin SC, Wang GS, Tsauer W, Hsu SF, Hsu SL (2002) Effector mechanisms of norcantharidin-induced mitotic arrest and apoptosis in human hepatoma cells. Int J Cancer 100(2):158–165PubMedCrossRef
32.
go back to reference Kok SH, Cheng SJ, Hong CY, Lee JJ, Lin SK, Kuo YS, Chiang CP, Kuo MY (2005) Norcantharidin-induced apoptosis in oral cancer cells is associated with an increase of proapoptotic to antiapoptotic protein ratio. Cancer Lett 217(1):43–52PubMedCrossRef Kok SH, Cheng SJ, Hong CY, Lee JJ, Lin SK, Kuo YS, Chiang CP, Kuo MY (2005) Norcantharidin-induced apoptosis in oral cancer cells is associated with an increase of proapoptotic to antiapoptotic protein ratio. Cancer Lett 217(1):43–52PubMedCrossRef
33.
go back to reference Kok SH, Hong CY, Kuo MY, Lee CH, Lee JJ, Lou IU, Lee MS, Hsiao M, Lin SK (2003) Comparisons of norcantharidin cytotoxic effects on oral cancer cells and normal buccal keratinocytes. Oral Oncol 39(1):19–26PubMedCrossRef Kok SH, Hong CY, Kuo MY, Lee CH, Lee JJ, Lou IU, Lee MS, Hsiao M, Lin SK (2003) Comparisons of norcantharidin cytotoxic effects on oral cancer cells and normal buccal keratinocytes. Oral Oncol 39(1):19–26PubMedCrossRef
34.
go back to reference Peng C, Liu X, Liu E, Xu K, Niu W, Chen R, Wang J, Zhang Z, Lin P, Wang J, Agrez M, Niu J (2009) Norcantharidin induces HT-29 colon cancer cell apoptosis through the alphavbeta6-extracellular signal-related kinase signaling pathway. Cancer Sci 100(12):2302–2308PubMedCrossRef Peng C, Liu X, Liu E, Xu K, Niu W, Chen R, Wang J, Zhang Z, Lin P, Wang J, Agrez M, Niu J (2009) Norcantharidin induces HT-29 colon cancer cell apoptosis through the alphavbeta6-extracellular signal-related kinase signaling pathway. Cancer Sci 100(12):2302–2308PubMedCrossRef
35.
go back to reference Bonness K, Aragon IV, Rutland B, Ofori-Acquah S, Dean NM, Honkanen RE (2006) Cantharidin-induced mitotic arrest is associated with the formation of aberrant mitotic spindles and lagging chromosomes resulting, in part, from the suppression of PP2A-alpha. Mol Cancer Ther 5(11):2727–2736PubMedCrossRef Bonness K, Aragon IV, Rutland B, Ofori-Acquah S, Dean NM, Honkanen RE (2006) Cantharidin-induced mitotic arrest is associated with the formation of aberrant mitotic spindles and lagging chromosomes resulting, in part, from the suppression of PP2A-alpha. Mol Cancer Ther 5(11):2727–2736PubMedCrossRef
36.
go back to reference Yang J, Wu J, Tan C, Klein PS (2003) PP2A:B56epsilon is required for Wnt/beta-catenin signaling during embryonic development. Development 130(23):5569–5578PubMedCrossRef Yang J, Wu J, Tan C, Klein PS (2003) PP2A:B56epsilon is required for Wnt/beta-catenin signaling during embryonic development. Development 130(23):5569–5578PubMedCrossRef
37.
go back to reference Li W, Xie L, Chen Z, Zhu Y, Sun Y, Miao Y, Xu Z, Han X (2010) Cantharidin, a potent and selective PP2A inhibitor, induces an oxidative stress-independent growth inhibition of pancreatic cancer cells through G2/M cell-cycle arrest and apoptosis. Cancer Sci 101(5):1226–1233PubMedCrossRef Li W, Xie L, Chen Z, Zhu Y, Sun Y, Miao Y, Xu Z, Han X (2010) Cantharidin, a potent and selective PP2A inhibitor, induces an oxidative stress-independent growth inhibition of pancreatic cancer cells through G2/M cell-cycle arrest and apoptosis. Cancer Sci 101(5):1226–1233PubMedCrossRef
38.
go back to reference Sakoff JA, Ackland SP, Baldwin ML, Keane MA, McCluskey A (2002) Anticancer activity and protein phosphatase 1 and 2A inhibition of a new generation of cantharidin analogues. Invest New Drugs 20(1):1–11PubMedCrossRef Sakoff JA, Ackland SP, Baldwin ML, Keane MA, McCluskey A (2002) Anticancer activity and protein phosphatase 1 and 2A inhibition of a new generation of cantharidin analogues. Invest New Drugs 20(1):1–11PubMedCrossRef
39.
go back to reference Cimmino F, Schulte JH, Zollo M, Koster J, Versteeg R, Iolascon A, Eggert A, Schramm A (2009) Galectin-1 is a major effector of TrkB-mediated neuroblastoma aggressiveness. Oncogene 28(19):2015–2023PubMedCrossRef Cimmino F, Schulte JH, Zollo M, Koster J, Versteeg R, Iolascon A, Eggert A, Schramm A (2009) Galectin-1 is a major effector of TrkB-mediated neuroblastoma aggressiveness. Oncogene 28(19):2015–2023PubMedCrossRef
40.
go back to reference Garzia L, Andolfo I, Cusanelli E, Marino N, Petrosino G, De Martino D, Esposito V, Galeone A, Navas L, Esposito S, Gargiulo S, Fattet S, Donofrio V, Cinalli G, Brunetti A, Vecchio LD, Northcott PA, Delattre O, Taylor MD, Iolascon A, Zollo M (2009) MicroRNA-199b-5p impairs cancer stem cells through negative regulation of HES1 in medulloblastoma. PloS One 4(3):e4998PubMedCrossRef Garzia L, Andolfo I, Cusanelli E, Marino N, Petrosino G, De Martino D, Esposito V, Galeone A, Navas L, Esposito S, Gargiulo S, Fattet S, Donofrio V, Cinalli G, Brunetti A, Vecchio LD, Northcott PA, Delattre O, Taylor MD, Iolascon A, Zollo M (2009) MicroRNA-199b-5p impairs cancer stem cells through negative regulation of HES1 in medulloblastoma. PloS One 4(3):e4998PubMedCrossRef
41.
go back to reference Yokota N, Mainprize TG, Taylor MD, Kohata T, Loreto M, Ueda S, Dura W, Grajkowska W, Kuo JS, Rutka JT (2004) Identification of differentially expressed and developmentally regulated genes in medulloblastoma using suppression subtraction hybridization. Oncogene 23(19):3444–3453PubMedCrossRef Yokota N, Mainprize TG, Taylor MD, Kohata T, Loreto M, Ueda S, Dura W, Grajkowska W, Kuo JS, Rutka JT (2004) Identification of differentially expressed and developmentally regulated genes in medulloblastoma using suppression subtraction hybridization. Oncogene 23(19):3444–3453PubMedCrossRef
42.
go back to reference van Noort M, Meeldijk J, van der Zee R, Destree O, Clevers H (2002) Wnt signaling controls the phosphorylation status of beta-catenin. J Biol Chem 277(20):17901–17905PubMedCrossRef van Noort M, Meeldijk J, van der Zee R, Destree O, Clevers H (2002) Wnt signaling controls the phosphorylation status of beta-catenin. J Biol Chem 277(20):17901–17905PubMedCrossRef
43.
go back to reference Massicot F, Dutertre-Catella H, Pham-Huy C, Liu XH, Duc HT, Warnet JM (2005) In vitro assessment of renal toxicity and inflammatory events of two protein phosphatase inhibitors cantharidin and nor-cantharidin. Basic Clin Pharmacol Toxicol 96(1):26–32PubMedCrossRef Massicot F, Dutertre-Catella H, Pham-Huy C, Liu XH, Duc HT, Warnet JM (2005) In vitro assessment of renal toxicity and inflammatory events of two protein phosphatase inhibitors cantharidin and nor-cantharidin. Basic Clin Pharmacol Toxicol 96(1):26–32PubMedCrossRef
44.
go back to reference Barker N, Clevers H (2006) Mining the Wnt pathway for cancer therapeutics. Nat Rev Drug Discov 5(12):997–1014PubMedCrossRef Barker N, Clevers H (2006) Mining the Wnt pathway for cancer therapeutics. Nat Rev Drug Discov 5(12):997–1014PubMedCrossRef
45.
go back to reference Baryawno N, Sveinbjornsson B, Kogner P, Johnsen JI (2010) Medulloblastoma: a disease with disorganized developmental signaling cascades. Cell Cycle 9(13):2548–2554PubMedCrossRef Baryawno N, Sveinbjornsson B, Kogner P, Johnsen JI (2010) Medulloblastoma: a disease with disorganized developmental signaling cascades. Cell Cycle 9(13):2548–2554PubMedCrossRef
46.
go back to reference Baryawno N, Sveinbjornsson B, Eksborg S, Chen CS, Kogner P, Johnsen JI (2010) Small-molecule inhibitors of phosphatidylinositol 3-kinase/Akt signaling inhibit Wnt/beta-catenin pathway cross-talk and suppress medulloblastoma growth. Cancer Res 70(1):266–276PubMedCrossRef Baryawno N, Sveinbjornsson B, Eksborg S, Chen CS, Kogner P, Johnsen JI (2010) Small-molecule inhibitors of phosphatidylinositol 3-kinase/Akt signaling inhibit Wnt/beta-catenin pathway cross-talk and suppress medulloblastoma growth. Cancer Res 70(1):266–276PubMedCrossRef
47.
go back to reference Widau RC, Jin Y, Dixon SA, Wadzinski BE, Gallagher PJ (2010) Protein phosphatase 2A (PP2A) holoenzymes regulate death-associated protein kinase (DAPK) in ceramide-induced anoikis. J Biol Chem 285(18):13827–13838PubMedCrossRef Widau RC, Jin Y, Dixon SA, Wadzinski BE, Gallagher PJ (2010) Protein phosphatase 2A (PP2A) holoenzymes regulate death-associated protein kinase (DAPK) in ceramide-induced anoikis. J Biol Chem 285(18):13827–13838PubMedCrossRef
48.
go back to reference Chen YJ, Shieh CJ, Tsai TH, Kuo CD, Ho LT, Liu TY, Liao HF (2005) Inhibitory effect of norcantharidin, a derivative compound from blister beetles, on tumor invasion and metastasis in CT26 colorectal adenocarcinoma cells. Anti-cancer drugs 16(3):293–299PubMedCrossRef Chen YJ, Shieh CJ, Tsai TH, Kuo CD, Ho LT, Liu TY, Liao HF (2005) Inhibitory effect of norcantharidin, a derivative compound from blister beetles, on tumor invasion and metastasis in CT26 colorectal adenocarcinoma cells. Anti-cancer drugs 16(3):293–299PubMedCrossRef
49.
go back to reference Chen YN, Cheng CC, Chen JC, Tsauer W, Hsu SL (2003) Norcantharidin-induced apoptosis is via the extracellular signal-regulated kinase and c-Jun-NH2-terminal kinase signaling pathways in human hepatoma HepG2 cells. Br J Pharmacol 140(3):461–470PubMedCrossRef Chen YN, Cheng CC, Chen JC, Tsauer W, Hsu SL (2003) Norcantharidin-induced apoptosis is via the extracellular signal-regulated kinase and c-Jun-NH2-terminal kinase signaling pathways in human hepatoma HepG2 cells. Br J Pharmacol 140(3):461–470PubMedCrossRef
50.
go back to reference Yang H, Guo W, Xu B, Li M, Cui J (2007) Anticancer activity and mechanisms of norcantharidin-Nd3II on hepatoma. Anticancer Drugs 18(10):1133–1137PubMedCrossRef Yang H, Guo W, Xu B, Li M, Cui J (2007) Anticancer activity and mechanisms of norcantharidin-Nd3II on hepatoma. Anticancer Drugs 18(10):1133–1137PubMedCrossRef
51.
go back to reference Chuang KA, Lieu CH, Tsai WJ, Wu MH, Chen YC, Liao JF, Wang CC, Kuo YC (2010) Evaluation of anti-Wnt/beta-catenin signaling agents by pGL4-TOP transfected stable cells with a luciferase reporter system. Braz J Med Biol Res 43(10):931–941PubMedCrossRef Chuang KA, Lieu CH, Tsai WJ, Wu MH, Chen YC, Liao JF, Wang CC, Kuo YC (2010) Evaluation of anti-Wnt/beta-catenin signaling agents by pGL4-TOP transfected stable cells with a luciferase reporter system. Braz J Med Biol Res 43(10):931–941PubMedCrossRef
52.
go back to reference Pizem J, Cort A, Zadravec-Zaletel L, Popovic M (2005) Survivin is a negative prognostic marker in medulloblastoma. Neuropathol Appl Neurobiol 31(4):422–428PubMedCrossRef Pizem J, Cort A, Zadravec-Zaletel L, Popovic M (2005) Survivin is a negative prognostic marker in medulloblastoma. Neuropathol Appl Neurobiol 31(4):422–428PubMedCrossRef
53.
go back to reference Mimeault M, Batra SK (2010) Frequent deregulations in the hedgehog signaling network and cross-talks with the epidermal growth factor receptor pathway involved in cancer progression and targeted therapies. Pharmacol Rev 62(3):497–524PubMedCrossRef Mimeault M, Batra SK (2010) Frequent deregulations in the hedgehog signaling network and cross-talks with the epidermal growth factor receptor pathway involved in cancer progression and targeted therapies. Pharmacol Rev 62(3):497–524PubMedCrossRef
54.
go back to reference Guo X, Wang XF (2009) Signaling cross-talk between TGF-beta/BMP and other pathways. Cell Res 19(1):71–88PubMedCrossRef Guo X, Wang XF (2009) Signaling cross-talk between TGF-beta/BMP and other pathways. Cell Res 19(1):71–88PubMedCrossRef
55.
go back to reference Li C, Zhang Y, Lu Y, Cui Z, Yu M, Zhang S, Xue X (2010) Evidence of the cross talk between Wnt and Notch signaling pathways in non-small-cell lung cancer (NSCLC): Notch3-siRNA weakens the effect of LiCl on the cell cycle of NSCLC cell lines. J Cancer Res Clin Oncol 5:771–778 Li C, Zhang Y, Lu Y, Cui Z, Yu M, Zhang S, Xue X (2010) Evidence of the cross talk between Wnt and Notch signaling pathways in non-small-cell lung cancer (NSCLC): Notch3-siRNA weakens the effect of LiCl on the cell cycle of NSCLC cell lines. J Cancer Res Clin Oncol 5:771–778
56.
go back to reference Orsulic S, Huber O, Aberle H, Arnold S, Kemler R (1999) E-cadherin binding prevents beta-catenin nuclear localization and beta-catenin/LEF-1-mediated transactivation. J Cell Sci 112(Pt 8):1237–1245PubMed Orsulic S, Huber O, Aberle H, Arnold S, Kemler R (1999) E-cadherin binding prevents beta-catenin nuclear localization and beta-catenin/LEF-1-mediated transactivation. J Cell Sci 112(Pt 8):1237–1245PubMed
57.
go back to reference Zhang L, Sun X, Zhang ZR (2005) An investigation on liver-targeting microemulsions of norcantharidin. Drug Deliv 12(5):289–295PubMedCrossRef Zhang L, Sun X, Zhang ZR (2005) An investigation on liver-targeting microemulsions of norcantharidin. Drug Deliv 12(5):289–295PubMedCrossRef
58.
go back to reference Malaterre J, Ramsay RG, Mantamadiotis T (2007) Wnt-Frizzled signalling and the many paths to neural development and adult brain homeostasis. Front Biosci 12:492–506PubMedCrossRef Malaterre J, Ramsay RG, Mantamadiotis T (2007) Wnt-Frizzled signalling and the many paths to neural development and adult brain homeostasis. Front Biosci 12:492–506PubMedCrossRef
59.
go back to reference Chenn A, Walsh CA (2002) Regulation of cerebral cortical size by control of cell cycle exit in neural precursors. Science 297(5580):365–369PubMedCrossRef Chenn A, Walsh CA (2002) Regulation of cerebral cortical size by control of cell cycle exit in neural precursors. Science 297(5580):365–369PubMedCrossRef
Metadata
Title
Norcantharidin impairs medulloblastoma growth by inhibition of Wnt/β-catenin signaling
Authors
Flora Cimmino
Maria Nunzia Scoppettuolo
Marianeve Carotenuto
Pasqualino De Antonellis
Valeria Di Dato
Gennaro De Vita
Massimo Zollo
Publication date
01-01-2012
Publisher
Springer US
Published in
Journal of Neuro-Oncology / Issue 1/2012
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-011-0645-y

Other articles of this Issue 1/2012

Journal of Neuro-Oncology 1/2012 Go to the issue