Journal of Neuro-Oncology

, Volume 124, Issue 1, pp 5–11 | Cite as

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

  • Fu-Rong Wang
  • Yong-Sheng Jiang
Laboratory Investigation


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.


Glioma Tumor growth Edema 


Conflict of interest

The authors declare that we have no conflict of interest.

Ethical standard

The experiments comply with the current laws of China.

Supplementary material

11060_2015_1804_MOESM1_ESM.doc (86 kb)
Supplementary material 1 (DOC 85 kb)


  1. 1.
    Fisher PG, Buffler PA (2005) Malignant gliomas in 2005: where to GO from here? JAMA 293:615–617PubMedCrossRefGoogle Scholar
  2. 2.
    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 110:1542–1550PubMedCrossRefGoogle Scholar
  3. 3.
    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 64:6892–6899PubMedCrossRefGoogle Scholar
  4. 4.
    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 352:987–996PubMedCrossRefGoogle Scholar
  5. 5.
    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 18:14PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    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 230:106–113PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    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 1:929–935PubMedGoogle Scholar
  8. 8.
    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 105:3312–3318PubMedCrossRefGoogle Scholar
  9. 9.
    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:e72927PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    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 43:1652–1658PubMedGoogle Scholar
  11. 11.
    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 2013:579751Google Scholar
  12. 12.
    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 53:325–333PubMedCrossRefGoogle Scholar
  13. 13.
    Parajuli P, Joshee N, Rimando AM, Mittal S, Yadav AK (2009) In vitro antitumor mechanisms of various Scutellaria extracts and constituent flavonoids. Planta Med 75:41–48PubMedCrossRefGoogle Scholar
  14. 14.
    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 37:118–129PubMedCrossRefGoogle Scholar
  15. 15.
    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 84:1107–1114PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    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 43:3368–3373PubMedGoogle Scholar
  17. 17.
    Nomura T, Inamura T, Black KL (1994) Intracarotid infusion of bradykinin selectively increases blood-tumor permeability in 9L and C6 brain tumors. Brain Res 659:62–66PubMedCrossRefGoogle Scholar
  18. 18.
    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 6:229–236PubMedCrossRefGoogle Scholar
  19. 19.
    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 112:1500–1512PubMedCrossRefGoogle Scholar
  20. 20.
    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 155:1279–1296PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    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 7:266–270PubMedGoogle Scholar
  22. 22.
    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 263:360–367PubMedCrossRefGoogle Scholar
  23. 23.
    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 10:459–466PubMedCrossRefGoogle Scholar
  24. 24.
    Papadopoulos MC, Saadoun S, Davies DC, Bell BA (2001) Emerging molecular mechanisms of brain tumour oedema. Br J Neurosurg 15:101–108PubMedCrossRefGoogle Scholar
  25. 25.
    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 11:939–948PubMedCrossRefGoogle Scholar
  26. 26.
    Seitz RJ, Wechsler W (1987) Immunohistochemical demonstration of serum proteins in human cerebral gliomas. Acta Neuropathol (Berl) 73:145–152CrossRefGoogle Scholar
  27. 27.
    Lee J, Baird A, Eliceiri BP (2011) In vivo measurement of glioma-induced vascular permeability. Methods Mol Biol 763:417–422PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    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) 104:85–91CrossRefGoogle Scholar
  29. 29.
    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–H440PubMedGoogle Scholar
  30. 30.
    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 127:210–216PubMedCrossRefGoogle Scholar
  31. 31.
    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 41:274–283PubMedCrossRefGoogle Scholar
  32. 32.
    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 18:6605–6613PubMedCentralPubMedCrossRefGoogle Scholar
  33. 33.
    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:e569PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Gandhi NM (2013) Baicalein protects mice against radiation-induced DNA damages and genotoxicity. Mol Cell Biochem 379:277–281PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Department of Neurology, Tongji Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
  2. 2.Department of Oncology, Tongji Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina

Personalised recommendations