Boswellic acid activity against glioblastoma stem-like cells

Schneider,Hannah; Weller,Michael

doi:10.3892/ol.2016.4516

Boswellic acid activity against glioblastoma stem-like cells

Authors:
- Hannah Schneider
- Michael Weller
View Affiliations

Affiliations: Laboratory of Molecular Neuro‑Oncology, Department of Neurology, University Hospital and University of Zurich, Zurich, Zurich 8091, Switzerland
Published online on: May 4, 2016 https://doi.org/10.3892/ol.2016.4516
Pages: 4187-4192

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Boswellic acids (BAs) have long been considered as useful adjunct pharmacological agents for the treatment of patients with malignant brain tumors, notably glioblastoma. Two principal modes of action associated with BAs have been postulated: i) Anti‑inflammatory properties, which are useful for containing edema formation, and ii) intrinsic antitumor cell properties, with a hitherto ill‑defined mode of action. The present study assessed the effects of various BA derivatives on the viability and clonogenicity of a panel of nine long‑term glioma cell lines and five glioma‑initiating cell lines, studied cell cycle progression and the mode of cell death induction, and explored potential synergy with temozolomide (TMZ) or irradiation. BA induced the concentration‑dependent loss of viability and clonogenicity that was independent of tumor protein 53 status and O6‑methylguanine DNA methyltransferase expression. The treatment of glioma cells with BA resulted in cell death induction, prior to or upon S phase entry, and exhibited features of apoptotic cell death. Synergy with irradiation or TMZ was detected at certain concentrations; however, the inhibitory effects were mostly additive, and never antagonistic. While the intrinsic cytotoxic properties of BA at low micromolecular concentrations were confirmed and the potential synergy with irradiation and TMZ was identified, the proximate pharmacodynamic target of BA remains to be identified.

View Figures

View References

1.	Kreck C and Saller R: Indischer Weihrauch und seine Zubereitungen einschliesslich H15 als traditionelles und modernes Therapeutikum. Internist Prax. 38:857–872. 1998.
2.	Abdel-Tawab M, Werz O and Schubert-Zsilavecz M: Boswellia serrata: An overall assessment of in vitro, preclinical, pharmacokinetic and clinical data. Clin Pharmacokinet. 50:349–369. 2011. View Article : Google Scholar : PubMed/NCBI
3.	Basch E, Boon H, Davies-Heerema T, Foppo I, Hashmi S, Hasskarl J, Sollars D and Ulbricht C: Boswellia: An evidence-based systematic review by the Natural Standard Research Collaboration. J Herb Pharmacother. 4:63–83. 2004. View Article : Google Scholar : PubMed/NCBI
4.	Gerbeth K, Meins J, Kirste S, Momm F, Schubert-Zsilavecz M and Abdel-Tawab M: Determination of major boswellic acids in plasma by high-pressure liquid chromatography/mass spectrometry. J Pharm Biomed Anal. 56:998–1005. 2011. View Article : Google Scholar : PubMed/NCBI
5.	Poeckel D and Werz O: Boswellic acids: Biological actions and molecular targets. Curr Med Chem. 13:3359–3369. 2006. View Article : Google Scholar : PubMed/NCBI
6.	Streffer JR, Bitzer M, Schabet M, Dichgans J and Weller M: Response of radiochemotherapy-associated cerebral edema to a phytotherapeutic agent, H15. Neurology. 56:1219–1221. 2001. View Article : Google Scholar : PubMed/NCBI
7.	Kirste S, Treier M, Wehrle SJ, Becker G, Abdel-Tawab M, Gerbeth K, Hug MJ, Lubrich B, Grosu AL and Momm F: Boswellia serrata acts on cerebral edema in patients irradiated for brain tumors: A prospective, randomized, placebo-controlled, double-blind pilot trial. Cancer. 117:3788–3795. 2011. View Article : Google Scholar : PubMed/NCBI
8.	Glaser T, Winter S, Groscurth P, Safayhi H, Sailer ER, Ammon HP, Schabet M and Weller M: Boswellic acids and malignant glioma: Induction of apoptosis but no modulation of drug sensitivity. Br J Cancer. 80:756–765. 1999. View Article : Google Scholar : PubMed/NCBI
9.	Winking M, Sarikaya S, Rahmanian A, Jödicke A and Böker DK: Boswellic acids inhibit glioma growth: A new treatment option? J Neurooncol. 46:97–103. 2000. View Article : Google Scholar : PubMed/NCBI
10.	Weller M, van den Bent M, Hopkins K, Tonn JC, Stupp R, Falini A, Cohen-Jonathan-Moyal E, Frappaz D, Henriksson R, Balana C, et al: EANO guideline for the diagnosis and treatment of anaplastic gliomas and glioblastoma. Lancet Oncol. 15:e395–e403. 2014. View Article : Google Scholar : PubMed/NCBI
11.	Günther HS, Schmidt NO, Phillips HS, Kemming D, Kharbanda S, Soriano R, Modrusan Z, Meissner H, Westphal M and Lamszus K: Glioblastoma-derived stem cell-enriched cultures form distinct subgroups according to molecular and phenotypic criteria. Oncogene. 27:2897–2909. 2008. View Article : Google Scholar : PubMed/NCBI
12.	Webb JL: Enzyme and Metabolic Inhibitors. 1:New York, NY: Academic Press. 55–79, and pp 488–512. 1963.
13.	Wischhusen J, Naumann U, Ohgaki H, Rastinejad F and Weller M: CP-31398, a novel p53-stabilizing agent, induces p53-dependent and p53-independent glioma cell death. Oncogene. 22:8233–8245. 2003. View Article : Google Scholar : PubMed/NCBI
14.	Hermisson M, Klumpp A, Wick W, Wischhusen J, Nagel G, Roos W, Kaina B and Weller M: O6-methylguanine DNA methyltransferase and p53 status predict temozolomide sensitivity in human malignant glioma cells. J Neurochem. 96:766–776. 2006. View Article : Google Scholar : PubMed/NCBI
15.	Gerbeth K, Hüsch J, Fricker G, Werz O, Schubert-Zsilavecz M and Abdel-Tawab M: In vitro metabolism, permeation and brain availability of six major boswellic acids from Boswellia serrata gum resins. Fitoterapia. 84:99–106. 2013. View Article : Google Scholar : PubMed/NCBI
16.	Reising K, Meins J, Bastian B, Eckert G, Mueller WE, Schubert-Zsilavecz M and Abdel-Tawab M: Determination of boswellic acids in brain and plasma by high-performance liquid chromatography/tandem mass spectrometry. Anal Chem. 77:6640–6645. 2005. View Article : Google Scholar : PubMed/NCBI
17.	Charles NA, Holland EC, Gilbertson R, Glass R and Kettenmann H: The brain tumor microenvironment. Glia. 59:1169–1180. 2011. View Article : Google Scholar : PubMed/NCBI
18.	Fujita M, Kohanbash G, Fellows-Mayle W, Hamilton RL, Komohara Y, Decker SA, Ohlfest JR and Okada H: COX-2 blockade suppresses gliomagenesis by inhibiting myeloid-derived suppressor cells. Cancer Res. 71:2664–2674. 2011. View Article : Google Scholar : PubMed/NCBI