Journal of Neuro-Oncology

, Volume 46, Issue 2, pp 97–103 | Cite as

Boswellic Acids Inhibit Glioma Growth: A New Treatment Option?

  • M. Winking
  • S. Sarikaya
  • A. Rahmanian
  • A. Jödicke
  • D.-K. Böker

Abstract

Conventional malignant glioma therapy (surgery, radiation therapy and chemotherapy) does not yield satisfying results. The prognosis of the glioma patient depends more on the histological grading of the tumor and patient's age than on the therapy. Especially the adjuvant chemotherapy failed to date to influence survival time in glioma patients significantly. To improve results in malignant glioma therapy additional therapeutic regimes are necessary.

In an earlier study we were able to show a significant reduction on perifocal edema by an extract from gum resin (EGR) accompanied with a clinical improvement in patients with malignant glioma. Also a decrease of urinary LTE4-excretion as a metabolite of leukotriene synthesis in brain tumors was observed. Furthermore we had found a proliferation inhibiting activity of the extract form EGR, the boswellic acids in cell cultures.

The purpose of this experimental study was to elucidate the effects of the boswellic acids, which are constituents of an extract from gum resin on tumor growth in vivo. Female wistar rats weighing 200–250 g were treated with the drug 14 days after inoculation of C6 tumor cells into their right caudate nucleus and randomization into 4 groups. The treatment groups received different dosages and were compared to a control group without any additional treatment. Survival time of the rats in the highest dosage group (3 × 240 mg/kg body weight) was more than twice as long as in the control group (P < 0.05).

In a second experiment the inhibition of tumor cell proliferation was examined. The C6 tumor cells were implanted into the caudate nucleus. Drug treatment was started immediately after implantation and stopped after 14 days. The animals were sacrificed and the brains were examined microscopically. Comparing low and high dosage of EGR treatment a significant difference in tumor volume was detected (P < 0.05). The proportion of apoptotic tumor cells in animals with high dose treatment was significantly larger than in the low dose (treatment) group (P < 0.05).

These data demonstrate an influence of EGR in rat glioma growth and might represent a new therapeutic option on glioma treatment in man in future. Further experimental work on human gliomas is needed to definitively answer this question.

boswellic acids glioma chemotherapy 

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References

  1. 1.
    Benda P, Lightbody J, Sato G, Levine L, Sweet W: Differentiated rat glial cell strain in tissue culture. Science 161: 370-371, 1968Google Scholar
  2. 2.
    Böker D-K, Winking M: Die Rolle von Boswellia-Säuren in der Therapie maligner Gliome. Dt. Ärztebl. 94: A-1197-1199, 1997Google Scholar
  3. 3.
    Bradbury M: The Concept of a Blood-Brain Barrier, J Wiley, New York, 1979Google Scholar
  4. 4.
    Fadul C, Wood J, Thaler H, Galicich J, Patterson RH, Posner JB: Morbidity and mortality of craniotomy for excision of supratentorial gliomas. Neurology 38: 1374-1379, 1988Google Scholar
  5. 5.
    Gavrieli Y, Sherman Y, Ben-Sasson SA: Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol 119: 493-501, 1992Google Scholar
  6. 6.
    Held RM, Syrovets T, Winking M, Seiler ER, Safayhi H, Ammon HPT, Simmet T: Boswellic acids exhibit cytotoxic effects on brain tumor cells independent form 5-ipoxygenase inhibition. Naunyn-Schmiedeberg's Archives of Pharmacology, 355(4): 15, 1996Google Scholar
  7. 7.
    Hochberg FH, Pruitt A: Assumptions in the radiotherapy of glioblastoma. Neurology 30: 907-911, 1980Google Scholar
  8. 8.
    Hoshino T: A commentary on the biology and growth kinetics of low-grade and high-grade gliomas. J Neurosurg 61: 895-900, 1984Google Scholar
  9. 9.
    Hoernlein RF, Orlikowsky F, Zehrer C: Acedtyl-11-ketoboswellic acid induces apoptosis in HL 60 and CCRF-CEM cells and inhibits topoisomerase I. Proc Am Assoc Canc Res 38: 1291, 1997Google Scholar
  10. 10.
    Jellinger K: Glioblastoma multiforme. Acta Neurochir 42: 5-32, 1978Google Scholar
  11. 11.
    Kapaln EL, Meier P: Nonparametric estimation from incomplete observations. J Am Stat Assoc 53: 457-481, 1958Google Scholar
  12. 12.
    Kiwak KJ, Moskowitz MA, Levine L: Leukotriene production in gerbil brain after ischemic insult, subarachnoid hemorrhage, and concussive injury. J Neurosurg 62: 865-869, 1985Google Scholar
  13. 13.
    Moskowitz MA, Kiwak KJ, Hekimian K, Levine L: Synthesis of compounds with properties of leukotrienes C4 and D4 in gerbil brains after ischemia and reperfusion. Science 224: 886-889, 1984Google Scholar
  14. 14.
    Piper PJ, Samhoun MN: Leukotrienes. Br Med Bull 43: 297-311, 1987Google Scholar
  15. 15.
    Rapoport SI: Blood-Brain Barrier in Physiology and Medicine. Raven Press, New York, 1976Google Scholar
  16. 16.
    Safayhi H, Mack T, Sabieraj J, Anazodo M, Subramanian LR, Ammon HPT: Boswellic Acids: Novel, specific, Nonredox Inhibitors of 5-Lipoxygenase. J Pharmakol and Experim Therap 261: 1143-1146, 1992Google Scholar
  17. 17.
    Samuelsson B, Dahlen SE, Lindgren JA, Rouzer CA, Serhan CN Leukotrienes and lipoxins: Structures, biosynthesis and biological effects. Science 237: 1171-1176, 1987Google Scholar
  18. 18.
    Shapiro WR: Treatment of neuroectodermal brain tumors. Ann Neurol 12: 231-237, 1982Google Scholar
  19. 19.
    Simmet T, Seregi A, Herting G: Formation of sulphidopeptide-leukotrienes by tissue of spontaneously convulsing gerbils. Neuropharmacology 26: 107-110, 1987Google Scholar
  20. 20.
    Simmet T, Luck W, Winking M, Delank WK, Peskar BA: Identification and characterization of cysteinyl-leukotriene formation in tissue slices from human intracranial tumors: evidence for their biosynthesis under in vivo conditions. J Neurochem 54: 2091-2099, 1990Google Scholar
  21. 21.
    Singh GB, Atal CK: Pharmacology of an extract of salai guggal extract Boswellia serrata, a new non-steroidal anti-inflammatory agent. Agents Actions 18: 407-412, 1986Google Scholar
  22. 22.
    Spencer CM, Faulds D: Paclitaxel, a review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in the treatment of cancer. Drugs 48: 794-847, 1994Google Scholar
  23. 23.
    Walker MD, Alexander E Jr, Hunt WE, MacCarty CS, Mahaley MS Jr, Mealey J Jr, Norell HA, Owens G, Ransohoff J, Wilson CB, Gehan EA, Strike TA: Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas: a cooperative clinical trial. J Neurosurg 48: L333-L343, 1978Google Scholar
  24. 24.
    Walker MD, Strike TA, Sheline GE: An analysis of doseeffect relationship in the radiotherapy of malignant gliomas. Int J Radiat Oncol Biol Phys 5: 1725-1731, 1979Google Scholar
  25. 25.
    Walker MD, Green SB, Byar DP: Randomized comparisons of radiotherapy and nitrosaureas for the treatment of malignant glioma after surgery. N Engl J Med 303: 1323-1329, 1980Google Scholar
  26. 26.
    Winking M, Lausberg G, Simmet T: Malignancy dependent formation of cysteinyl-leukotrienes in human brain tumor tissues and its detection in urine. In: Piscol K, Brock M, Klinger M (eds) Advances in Neurosurgery Vol 20, 1992Google Scholar
  27. 27.
    Winking M, Boeker DK, Simmet T: Blood-brain cell contact triggers leukotriene formation in brain cells via thrombin. J Cereb Blood Flow Metab 15(Suppl 1): 700, 1995Google Scholar
  28. 28.
    Winking M, Böker DK, Simmet Th: Boswellic acid as an inhibitor of the perifocal edema in malignant glioma in man. Neurooncol. 30: P39, 1996Google Scholar
  29. 29.
    Winking M, Heldt RM, Simmet T: Thrombin is the Stimulus Liable for Activation of the Cerebral 5-Lipoxygenase Pathway during Blood-Brain Cell Contact. J Cereb Blood Flow Metab 16: 737-745, 1996Google Scholar
  30. 30.
    Winking M, Müller H, Deinsberger W, Jödicke A, Böker DK: Levels of immunoreactive Cysteinyl-Leukotrienes after subarachnoid hemorrhage correlate with the blood-velocity in TCD. Acta Neurochir 139: 764-769, 1997Google Scholar
  31. 31.
    Winking M, Deinsberger W, Jöedicke A, Böeker DK: Cysteinyl-Leukotriene levels in intracerebral hemorrhage-an edema promoting factor? Cerebrovasc Dis 8: 316-326, 1998Google Scholar

Copyright information

© Kluwer Academic Publishers 2000

Authors and Affiliations

  • M. Winking
    • 1
  • S. Sarikaya
    • 1
  • A. Rahmanian
    • 1
  • A. Jödicke
    • 1
  • D.-K. Böker
    • 1
  1. 1.Neurosurgical ClinicJustus-Liebig University GiessenGiessenGermany

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