Boswellic acid formulations are not suitable for treatment of pediatric high-grade glioma due to tumor promoting potential

Maria Wiese; Bente Pohlmeier; Klaudia Kubiak; Fatma E El-Khouly; Maren Sitte; Angel M Carcaboso; Joshua N Baugh; Thomas Perwein; Gunther Nussbaumer; Michael Karremann; Gerrit H Gielen; Gabriela Salinas; Christof M Kramm

doi:10.1016/j.jtcme.2023.07.007

Boswellic acid formulations are not suitable for treatment of pediatric high-grade glioma due to tumor promoting potential

J Tradit Complement Med. 2023 Jul 25;14(1):101-108. doi: 10.1016/j.jtcme.2023.07.007. eCollection 2024 Jan.

Authors

Affiliations

¹ Division of Pediatric Hematology and Oncology, Department of Child and Adolescent Health, University Medical Center Goettingen, Robert Koch Straße 40, Goettingen, Germany.
² Pediatric Oncology, Emma Children's Hospital, Amsterdam UMC, De Boelelaan 1118 Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
³ Transcriptome and Genome Analysis Laboratory (TAL), Department of Developmental Biochemistry, University Medical Center Goettingen, Justus-von-Liebig-Weg 11, Goettingen, Germany.
⁴ Pediatric Hematology and Oncology, Hospital Sant Joan de Deu/Institut de Recerca, Sant Joan de Deu 2, Barcelona, Spain.
⁵ Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
⁶ Division of Pediatric Hematology-Oncology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Auenbruggerplatz 38, Graz, Austria.
⁷ Institute of Neuropathology, University Hospital Bonn, Venusberg-Campus 1, Bonn, Germany.

Abstract

Background and aim: Pediatric high-grade gliomas (pedHGG) comprise a very poor prognosis. Thus, parents of affected children are increasingly resorting to complementary and alternative medicine (CAM), among those Boswellia extracts. However, nothing is known about the therapeutic effectiveness of their active substances, Boswellic acids (BA) in pedHGG. Thus, we aimed to investigate if the three main Boswellic acids (BA) present in Boswellia plants, alpha-boswellic acid (α-BA), beta-boswellic acid (β-BA) and 3-acetyl-11-keto-beta-boswellic acid (AKBA) hold any promising potential for treatment of affected pedHGG patients.

Experimental procedure: Histone 3 (H3)-wildtype and H3.3K27M-mutant pedHGG cell lines were treated with BA, either alone or in combination with radio-chemotherapy with temozolomide. Cell viability, stemness properties, apoptosis, in ovo tumor growth and the transcriptome was investigated upon BA treatment.

Results and conclusion: Interestingly, α-BA and β-BA treatment promoted certain tumor properties in both pedHGG cells. AKBA treatment reduced cell viability and colony growth accompanied by induction of slight anti-inflammatory effects especially in H3.3K27M-mutant pedHGG cells. However, no effects on apoptosis and in ovo tumor growth were found. In conclusion, besides positive anti-tumor effects of AKBA, tumor promoting effects were observed upon treatment with α-BA and β-BA. Thus, only pure AKBA formulations may be used to exploit any potential positive effects in pedHGG patients. In conclusion, the use of commercially available supplements with a mixture of different BA cannot be recommended due to detrimental effects of certain BA whereas pure AKBA formulations might hold some potential as therapeutic supplement for treatment of pedHGG patients.

Keywords: 3-Acetyl-11-keto-beta-boswellic acid (AKBA); Alpha-boswellic acid (α-BA); Beta-boswellic acid (β-BA); Complementary and alternative medicine (CAM); Diffuse intrinsic pontine glioma (DIPG).