Skip to main content
Top
Published in: Journal of Neuro-Oncology 1/2015

01-08-2015 | Laboratory Investigation

Effect of treatment with baicalein on the intracerebral tumor growth and survival of orthotopic glioma models

Authors: Fu-Rong Wang, Yong-Sheng Jiang

Published in: Journal of Neuro-Oncology | Issue 1/2015

Login to get access

Abstract

Baicalein, a widely used Chinese herbal medicine, has been proved as a promising chemopreventive compound for many cancers. The aim of this work was to assess the anti-tumor effect of baicalein in the orthotopic glioma models. It was found that treatment of mice with U87 gliomas with baicalein (20 and 40 mg/kg/day, i.p.) significantly inhibited the intracerebral tumor growth and prolonged the survival. Furthermore, treatment with baicalein suppressed cell proliferation, promoted apoptosis, and arrested cell cycle in U87 gliomas. In addition, treatment with baicalein reduced tumor permeability, attenuated edema of tumors and brains, and improved tight junctions in gliomas. Finally, treatment with baicalein reduced the expression of HIF-1α, VEGF, and VEGFR2 in U87 gliomas. In addition, treatment with baicalein also markedly suppressed tumor growth and prolonged the survival of rats with 9L gliomas. In conclusion, baicalein has an obvious anti-tumor activity in the orthotopic glioma models. Our results suggested that treatment with baicalein might be an effective therapy for recurrent malignant brain cancers through suppressing tumor growth and alleviating edema.
Appendix
Available only for authorised users
Literature
1.
2.
go back to reference Nicholson HS, Kretschmar CS, Krailo M, Bernstein M, Kadota R, Fort D, Friedman H, Harris MB, Tedeschi-Blok N, Mazewski C, Sato J, Reaman GH (2007) Phase 2 study of temozolomide in children and adolescents with recurrent central nervous system tumors: a report from the Children’s Oncology Group. Cancer 110:1542–1550PubMedCrossRef Nicholson HS, Kretschmar CS, Krailo M, Bernstein M, Kadota R, Fort D, Friedman H, Harris MB, Tedeschi-Blok N, Mazewski C, Sato J, Reaman GH (2007) Phase 2 study of temozolomide in children and adolescents with recurrent central nervous system tumors: a report from the Children’s Oncology Group. Cancer 110:1542–1550PubMedCrossRef
3.
go back to reference Ohgaki H, Dessen P, Jourde B, Horstmann S, Nishikawa T, Di Patre PL, Burkhard C, Schuler D, Probst-Hensch NM, Maiorka PC, Baeza N, Pisani P, Yonekawa Y, Yasargil MG, Lutolf UM, Kleihues P (2004) Genetic pathways to glioblastoma: a population-based study. Cancer Res 64:6892–6899PubMedCrossRef Ohgaki H, Dessen P, Jourde B, Horstmann S, Nishikawa T, Di Patre PL, Burkhard C, Schuler D, Probst-Hensch NM, Maiorka PC, Baeza N, Pisani P, Yonekawa Y, Yasargil MG, Lutolf UM, Kleihues P (2004) Genetic pathways to glioblastoma: a population-based study. Cancer Res 64:6892–6899PubMedCrossRef
4.
go back to reference Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996PubMedCrossRef Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996PubMedCrossRef
5.
go back to reference Jeong K, Shin YC, Park S, Park JS, Kim N, Um JY, Go H, Sun S, Lee S, Park W, Choi Y, Song Y, Kim G, Jeon C, Park J, Lee K, Bang O, Ko SG (2011) Ethanol extract of Scutellaria baicalensis Georgi prevents oxidative damage and neuroinflammation and memorial impairments in artificial senescense mice. J Biomed Sci 18:14PubMedCentralPubMedCrossRef Jeong K, Shin YC, Park S, Park JS, Kim N, Um JY, Go H, Sun S, Lee S, Park W, Choi Y, Song Y, Kim G, Jeon C, Park J, Lee K, Bang O, Ko SG (2011) Ethanol extract of Scutellaria baicalensis Georgi prevents oxidative damage and neuroinflammation and memorial impairments in artificial senescense mice. J Biomed Sci 18:14PubMedCentralPubMedCrossRef
6.
go back to reference Stavniichuk R, Drel VR, Shevalye H, Maksimchyk Y, Kuchmerovska TM, Nadler JL, Obrosova IG (2011) Baicalein alleviates diabetic peripheral neuropathy through inhibition of oxidative-nitrosative stress and p38 MAPK activation. Exp Neurol 230:106–113PubMedCentralPubMedCrossRef Stavniichuk R, Drel VR, Shevalye H, Maksimchyk Y, Kuchmerovska TM, Nadler JL, Obrosova IG (2011) Baicalein alleviates diabetic peripheral neuropathy through inhibition of oxidative-nitrosative stress and p38 MAPK activation. Exp Neurol 230:106–113PubMedCentralPubMedCrossRef
7.
go back to reference Tong WG, Ding XZ, Witt RC, Adrian TE (2002) Lipoxygenase inhibitors attenuate growth of human pancreatic cancer xenografts and induce apoptosis through the mitochondrial pathway. Mol Cancer Ther 1:929–935PubMed Tong WG, Ding XZ, Witt RC, Adrian TE (2002) Lipoxygenase inhibitors attenuate growth of human pancreatic cancer xenografts and induce apoptosis through the mitochondrial pathway. Mol Cancer Ther 1:929–935PubMed
8.
go back to reference Ma Z, Otsuyama K, Liu S, Abroun S, Ishikawa H, Tsuyama N, Obata M, Li FJ, Zheng X, Maki Y, Miyamoto K, Kawano MM (2005) Baicalein, a component of Scutellaria radix from Huang-Lian-Jie-Du-Tang (HLJDT), leads to suppression of proliferation and induction of apoptosis in human myeloma cells. Blood 105:3312–3318PubMedCrossRef Ma Z, Otsuyama K, Liu S, Abroun S, Ishikawa H, Tsuyama N, Obata M, Li FJ, Zheng X, Maki Y, Miyamoto K, Kawano MM (2005) Baicalein, a component of Scutellaria radix from Huang-Lian-Jie-Du-Tang (HLJDT), leads to suppression of proliferation and induction of apoptosis in human myeloma cells. Blood 105:3312–3318PubMedCrossRef
9.
go back to reference Chen K, Zhang S, Ji Y, Li J, An P, Ren H, Liang R, Yang J, Li Z (2013) Baicalein inhibits the invasion and metastatic capabilities of hepatocellular carcinoma cells via down-regulation of the ERK pathway. PLoS One 8:e72927PubMedCentralPubMedCrossRef Chen K, Zhang S, Ji Y, Li J, An P, Ren H, Liang R, Yang J, Li Z (2013) Baicalein inhibits the invasion and metastatic capabilities of hepatocellular carcinoma cells via down-regulation of the ERK pathway. PLoS One 8:e72927PubMedCentralPubMedCrossRef
10.
go back to reference Kim DH, Hossain MA, Kang YJ, Jang JY, Lee YJ, Im E, Yoon JH, Kim HS, Chung HY, Kim ND (2013) Baicalein, an active component of Scutellaria baicalensis Georgi, induces apoptosis in human colon cancer cells and prevents AOM/DSS-induced colon cancer in mice. Int J Oncol 43:1652–1658PubMed Kim DH, Hossain MA, Kang YJ, Jang JY, Lee YJ, Im E, Yoon JH, Kim HS, Chung HY, Kim ND (2013) Baicalein, an active component of Scutellaria baicalensis Georgi, induces apoptosis in human colon cancer cells and prevents AOM/DSS-induced colon cancer in mice. Int J Oncol 43:1652–1658PubMed
11.
go back to reference Wu JY, Tsai KW, Li YZ, Chang YS, Lai YC, Laio YH, Wu JD, Liu YW (2013) Anti-bladder-tumor effect of baicalein from Scutellaria baicalensis Georgi and its application in vivo. Evid Based Complement Altern Med 2013:579751 Wu JY, Tsai KW, Li YZ, Chang YS, Lai YC, Laio YH, Wu JD, Liu YW (2013) Anti-bladder-tumor effect of baicalein from Scutellaria baicalensis Georgi and its application in vivo. Evid Based Complement Altern Med 2013:579751
12.
go back to reference Zhang Y, Song L, Cai L, Wei R, Hu H, Jin W (2013) Effects of baicalein on apoptosis, cell cycle arrest, migration and invasion of osteosarcoma cells. Food Chem Toxicol 53:325–333PubMedCrossRef Zhang Y, Song L, Cai L, Wei R, Hu H, Jin W (2013) Effects of baicalein on apoptosis, cell cycle arrest, migration and invasion of osteosarcoma cells. Food Chem Toxicol 53:325–333PubMedCrossRef
13.
go back to reference Parajuli P, Joshee N, Rimando AM, Mittal S, Yadav AK (2009) In vitro antitumor mechanisms of various Scutellaria extracts and constituent flavonoids. Planta Med 75:41–48PubMedCrossRef Parajuli P, Joshee N, Rimando AM, Mittal S, Yadav AK (2009) In vitro antitumor mechanisms of various Scutellaria extracts and constituent flavonoids. Planta Med 75:41–48PubMedCrossRef
14.
go back to reference Chiu WT, Shen SC, Chow JM, Lin CW, Shia LT, Chen YC (2010) Contribution of reactive oxygen species to migration/invasion of human glioblastoma cells U87 via ERK-dependent COX-2/PGE(2) activation. Neurobiol Dis 37:118–129PubMedCrossRef Chiu WT, Shen SC, Chow JM, Lin CW, Shia LT, Chen YC (2010) Contribution of reactive oxygen species to migration/invasion of human glioblastoma cells U87 via ERK-dependent COX-2/PGE(2) activation. Neurobiol Dis 37:118–129PubMedCrossRef
15.
go back to reference Ranes MK, El-Abbadi M, Manfredi MG, Mukherjee P, Platt FM, Seyfried TN (2001) N-butyldeoxynojirimycin reduces growth and ganglioside content of experimental mouse brain tumours. Br J Cancer 84:1107–1114PubMedCentralPubMedCrossRef Ranes MK, El-Abbadi M, Manfredi MG, Mukherjee P, Platt FM, Seyfried TN (2001) N-butyldeoxynojirimycin reduces growth and ganglioside content of experimental mouse brain tumours. Br J Cancer 84:1107–1114PubMedCentralPubMedCrossRef
16.
go back to reference Groothuis DR, Fischer JM, Pasternak JF, Blasberg RG, Vick NA, Bigner DD (1983) Regional measurements of blood-to-tissue transport in experimental RG-2 rat gliomas. Cancer Res 43:3368–3373PubMed Groothuis DR, Fischer JM, Pasternak JF, Blasberg RG, Vick NA, Bigner DD (1983) Regional measurements of blood-to-tissue transport in experimental RG-2 rat gliomas. Cancer Res 43:3368–3373PubMed
17.
go back to reference Nomura T, Inamura T, Black KL (1994) Intracarotid infusion of bradykinin selectively increases blood-tumor permeability in 9L and C6 brain tumors. Brain Res 659:62–66PubMedCrossRef Nomura T, Inamura T, Black KL (1994) Intracarotid infusion of bradykinin selectively increases blood-tumor permeability in 9L and C6 brain tumors. Brain Res 659:62–66PubMedCrossRef
18.
go back to reference Gerstner ER, Duda DG, di Tomaso E, Ryg PA, Loeffler JS, Sorensen AG, Ivy P, Jain RK, Batchelor TT (2009) VEGF inhibitors in the treatment of cerebral edema in patients with brain cancer. Nat Rev Clin Oncol 6:229–236PubMedCrossRef Gerstner ER, Duda DG, di Tomaso E, Ryg PA, Loeffler JS, Sorensen AG, Ivy P, Jain RK, Batchelor TT (2009) VEGF inhibitors in the treatment of cerebral edema in patients with brain cancer. Nat Rev Clin Oncol 6:229–236PubMedCrossRef
19.
go back to reference Liu C, Wu J, Xu K, Cai F, Gu J, Ma L, Chen J (2010) Neuroprotection by baicalein in ischemic brain injury involves PTEN/AKT pathway. J Neurochem 112:1500–1512PubMedCrossRef Liu C, Wu J, Xu K, Cai F, Gu J, Ma L, Chen J (2010) Neuroprotection by baicalein in ischemic brain injury involves PTEN/AKT pathway. J Neurochem 112:1500–1512PubMedCrossRef
20.
go back to reference Chen SF, Hsu CW, Huang WH, Wang JY (2008) Post-injury baicalein improves histological and functional outcomes and reduces inflammatory cytokines after experimental traumatic brain injury. Br J Pharmacol 155:1279–1296PubMedCentralPubMedCrossRef Chen SF, Hsu CW, Huang WH, Wang JY (2008) Post-injury baicalein improves histological and functional outcomes and reduces inflammatory cytokines after experimental traumatic brain injury. Br J Pharmacol 155:1279–1296PubMedCentralPubMedCrossRef
21.
go back to reference Li HL, Zhang S, Wang Y, Liang RR, Li J, An P, Wang ZM, Yang J, Li ZF (2013) Baicalein induces apoptosis via a mitochondrial-dependent caspase activation pathway in T24 bladder cancer cells. Mol Med Rep 7:266–270PubMed Li HL, Zhang S, Wang Y, Liang RR, Li J, An P, Wang ZM, Yang J, Li ZF (2013) Baicalein induces apoptosis via a mitochondrial-dependent caspase activation pathway in T24 bladder cancer cells. Mol Med Rep 7:266–270PubMed
22.
go back to reference Cheng YH, Li LA, Lin P, Cheng LC, Hung CH, Chang NW, Lin C (2012) Baicalein induces G1 arrest in oral cancer cells by enhancing the degradation of cyclin D1 and activating AhR to decrease Rb phosphorylation. Toxicol Appl Pharmacol 263:360–367PubMedCrossRef Cheng YH, Li LA, Lin P, Cheng LC, Hung CH, Chang NW, Lin C (2012) Baicalein induces G1 arrest in oral cancer cells by enhancing the degradation of cyclin D1 and activating AhR to decrease Rb phosphorylation. Toxicol Appl Pharmacol 263:360–367PubMedCrossRef
23.
go back to reference Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K, Hau P, Brandes AA, Gijtenbeek J, Marosi C, Vecht CJ, Mokhtari K, Wesseling P, Villa S, Eisenhauer E, Gorlia T, Weller M, Lacombe D, Cairncross JG, Mirimanoff RO, European Organisation for Research and Treatment of Cancer Brain Tumour and Radiation Oncology Groups; National Cancer Institute of Canada Clinical Trials Group (2009) Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 10:459–466PubMedCrossRef Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K, Hau P, Brandes AA, Gijtenbeek J, Marosi C, Vecht CJ, Mokhtari K, Wesseling P, Villa S, Eisenhauer E, Gorlia T, Weller M, Lacombe D, Cairncross JG, Mirimanoff RO, European Organisation for Research and Treatment of Cancer Brain Tumour and Radiation Oncology Groups; National Cancer Institute of Canada Clinical Trials Group (2009) Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 10:459–466PubMedCrossRef
24.
go back to reference Papadopoulos MC, Saadoun S, Davies DC, Bell BA (2001) Emerging molecular mechanisms of brain tumour oedema. Br J Neurosurg 15:101–108PubMedCrossRef Papadopoulos MC, Saadoun S, Davies DC, Bell BA (2001) Emerging molecular mechanisms of brain tumour oedema. Br J Neurosurg 15:101–108PubMedCrossRef
25.
go back to reference Groothuis DR, Lapin GD, Vriesendorp FJ, Mikhael MA, Patlak CS (1991) A method to quantitatively measure transcapillary transport of iodinated compounds in canine brain tumors with computed tomography. J Cereb Blood Flow Metab 11:939–948PubMedCrossRef Groothuis DR, Lapin GD, Vriesendorp FJ, Mikhael MA, Patlak CS (1991) A method to quantitatively measure transcapillary transport of iodinated compounds in canine brain tumors with computed tomography. J Cereb Blood Flow Metab 11:939–948PubMedCrossRef
26.
go back to reference Seitz RJ, Wechsler W (1987) Immunohistochemical demonstration of serum proteins in human cerebral gliomas. Acta Neuropathol (Berl) 73:145–152CrossRef Seitz RJ, Wechsler W (1987) Immunohistochemical demonstration of serum proteins in human cerebral gliomas. Acta Neuropathol (Berl) 73:145–152CrossRef
28.
go back to reference Rascher G, Fischmann A, Kroger S, Duffner F, Grote EH, Wolburg H (2002) Extracellular matrix and the blood-brain barrier in glioblastoma multiforme: spatial segregation of tenascin and agrin. Acta Neuropathol (Berl) 104:85–91CrossRef Rascher G, Fischmann A, Kroger S, Duffner F, Grote EH, Wolburg H (2002) Extracellular matrix and the blood-brain barrier in glioblastoma multiforme: spatial segregation of tenascin and agrin. Acta Neuropathol (Berl) 104:85–91CrossRef
29.
go back to reference Wang W, Dentler WL, Borchardt RT (2001) VEGF increases BMEC monolayer permeability by affecting occludin expression and tight junction assembly. Am J Physiol Heart Circ Physiol 280:H434–H440PubMed Wang W, Dentler WL, Borchardt RT (2001) VEGF increases BMEC monolayer permeability by affecting occludin expression and tight junction assembly. Am J Physiol Heart Circ Physiol 280:H434–H440PubMed
30.
go back to reference Herr D, Sallmann A, Bekes I, Konrad R, Holzheu I, Kreienberg R, Wulff C (2012) VEGF induces ascites in ovarian cancer patients via increasing peritoneal permeability by downregulation of Claudin 5. Gynecol Oncol 127:210–216PubMedCrossRef Herr D, Sallmann A, Bekes I, Konrad R, Holzheu I, Kreienberg R, Wulff C (2012) VEGF induces ascites in ovarian cancer patients via increasing peritoneal permeability by downregulation of Claudin 5. Gynecol Oncol 127:210–216PubMedCrossRef
31.
go back to reference Schmitt M, Horbach A, Kubitz R, Frilling A, Häussinger D (2004) Disruption of hepatocellular tight junctions by vascular endothelial growth factor (VEGF): a novel mechanism for tumor invasion. J Hepatol 41:274–283PubMedCrossRef Schmitt M, Horbach A, Kubitz R, Frilling A, Häussinger D (2004) Disruption of hepatocellular tight junctions by vascular endothelial growth factor (VEGF): a novel mechanism for tumor invasion. J Hepatol 41:274–283PubMedCrossRef
32.
go back to reference Huang HL, Wang YJ, Zhang QY, Liu B, Wang FY, Li JJ, Zhu RZ (2012) Hepatoprotective effects of baicalein against CCl4-induced acute liver injury in mice. World J Gastroenterol 18:6605–6613PubMedCentralPubMedCrossRef Huang HL, Wang YJ, Zhang QY, Liu B, Wang FY, Li JJ, Zhu RZ (2012) Hepatoprotective effects of baicalein against CCl4-induced acute liver injury in mice. World J Gastroenterol 18:6605–6613PubMedCentralPubMedCrossRef
33.
go back to reference Xu J, Zhang Y, Xiao Y, Ma S, Liu Q, Dang S, Jin M, Shi Y, Wan B, Zhang Y (2013) Inhibition of 12/15-lipoxygenase by baicalein induces microglia PPARβ/δ: a potential therapeutic role for CNS autoimmune disease. Cell Death Dis 4:e569PubMedCentralPubMedCrossRef Xu J, Zhang Y, Xiao Y, Ma S, Liu Q, Dang S, Jin M, Shi Y, Wan B, Zhang Y (2013) Inhibition of 12/15-lipoxygenase by baicalein induces microglia PPARβ/δ: a potential therapeutic role for CNS autoimmune disease. Cell Death Dis 4:e569PubMedCentralPubMedCrossRef
34.
go back to reference Gandhi NM (2013) Baicalein protects mice against radiation-induced DNA damages and genotoxicity. Mol Cell Biochem 379:277–281PubMedCrossRef Gandhi NM (2013) Baicalein protects mice against radiation-induced DNA damages and genotoxicity. Mol Cell Biochem 379:277–281PubMedCrossRef
Metadata
Title
Effect of treatment with baicalein on the intracerebral tumor growth and survival of orthotopic glioma models
Authors
Fu-Rong Wang
Yong-Sheng Jiang
Publication date
01-08-2015
Publisher
Springer US
Published in
Journal of Neuro-Oncology / Issue 1/2015
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-015-1804-3

Other articles of this Issue 1/2015

Journal of Neuro-Oncology 1/2015 Go to the issue