Skip to main content

Advertisement

Log in

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

  • Laboratory Investigation
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Fisher PG, Buffler PA (2005) Malignant gliomas in 2005: where to GO from here? JAMA 293:615–617

    Article  CAS  PubMed  Google Scholar 

  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 110:1542–1550

    Article  CAS  PubMed  Google Scholar 

  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 64:6892–6899

    Article  CAS  PubMed  Google Scholar 

  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 352:987–996

    Article  CAS  PubMed  Google Scholar 

  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 18:14

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 230:106–113

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 1:929–935

    CAS  PubMed  Google Scholar 

  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 105:3312–3318

    Article  CAS  PubMed  Google Scholar 

  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:e72927

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 43:1652–1658

    CAS  PubMed  Google Scholar 

  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 2013:579751

    Google Scholar 

  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 53:325–333

    Article  CAS  PubMed  Google Scholar 

  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 75:41–48

    Article  CAS  PubMed  Google Scholar 

  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 37:118–129

    Article  CAS  PubMed  Google Scholar 

  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 84:1107–1114

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 43:3368–3373

    CAS  PubMed  Google Scholar 

  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 659:62–66

    Article  CAS  PubMed  Google Scholar 

  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 6:229–236

    Article  CAS  PubMed  Google Scholar 

  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 112:1500–1512

    Article  CAS  PubMed  Google Scholar 

  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 155:1279–1296

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 7:266–270

    CAS  PubMed  Google Scholar 

  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 263:360–367

    Article  CAS  PubMed  Google Scholar 

  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 10:459–466

    Article  CAS  PubMed  Google Scholar 

  24. Papadopoulos MC, Saadoun S, Davies DC, Bell BA (2001) Emerging molecular mechanisms of brain tumour oedema. Br J Neurosurg 15:101–108

    Article  CAS  PubMed  Google Scholar 

  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 11:939–948

    Article  CAS  PubMed  Google Scholar 

  26. Seitz RJ, Wechsler W (1987) Immunohistochemical demonstration of serum proteins in human cerebral gliomas. Acta Neuropathol (Berl) 73:145–152

    Article  CAS  Google Scholar 

  27. Lee J, Baird A, Eliceiri BP (2011) In vivo measurement of glioma-induced vascular permeability. Methods Mol Biol 763:417–422

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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) 104:85–91

    Article  CAS  Google Scholar 

  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–H440

    CAS  PubMed  Google Scholar 

  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 127:210–216

    Article  CAS  PubMed  Google Scholar 

  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 41:274–283

    Article  CAS  PubMed  Google Scholar 

  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 18:6605–6613

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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:e569

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Gandhi NM (2013) Baicalein protects mice against radiation-induced DNA damages and genotoxicity. Mol Cell Biochem 379:277–281

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

The authors declare that we have no conflict of interest.

Ethical standard

The experiments comply with the current laws of China.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yong-Sheng Jiang.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 85 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, FR., Jiang, YS. Effect of treatment with baicalein on the intracerebral tumor growth and survival of orthotopic glioma models. J Neurooncol 124, 5–11 (2015). https://doi.org/10.1007/s11060-015-1804-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-015-1804-3

Keywords

Navigation