Perspectives on the use of flavonoids in glioblastoma treatment by targeting adenosine receptors

Katrin Sak

Exploration of Neuroscience ›› 2026, Vol. 5 ›› Issue (1) : 1006122

PDF (738KB)
Exploration of Neuroscience ›› 2026, Vol. 5 ›› Issue (1) :1006122 DOI: 10.37349/en.2026.1006122
research-article
Perspectives on the use of flavonoids in glioblastoma treatment by targeting adenosine receptors
Author information +
History +
PDF (738KB)

Abstract

Flavonoids are a large class of natural polyphenolic substances ubiquitously synthesized in the plant kingdom. When entering the human body, these compounds can exert a wide range of biological activities, including immunomodulatory, antiinflammatory, and anticancer effects. Over the recent years, the mechanisms underlying these actions have become increasingly clear, also indicating the important involvement of G protein-coupled receptors (GPCRs), such as adenosine receptors, in signal transduction networks. In this perspective article, the potential role of flavonoids as adenosine receptor antagonists on the development, progression, and spread of glioblastoma is discussed, blocking the tumor-promoting and immunosuppressive actions of elevated levels of endogenous adenosine. Therefore, flavonoids can be considered as structural leads for developing novel antiglioblastoma agents, applied either alone or as boosters of chemo- or immunotherapy to improve the quality of life and outcome of patients. The importance of these studies is, in turn, emphasized by the current lack of effective treatment strategies for this highly aggressive and fast-growing brain tumor, associated with poor prognosis.

Keywords

brain tumors / glioblastoma / targeted therapy / adenosine receptors / antagonists / phytochemicals / flavonoids

Cite this article

Download citation ▾
Katrin Sak. Perspectives on the use of flavonoids in glioblastoma treatment by targeting adenosine receptors. Exploration of Neuroscience, 2026, 5 (1) : 1006122 DOI:10.37349/en.2026.1006122

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al.Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024; 74:229-63.

[2]

Bova V, Filippone A, Casili G, Lanza M, Campolo M, Capra AP, et al.Adenosine Targeting as a New Strategy to Decrease Glioblastoma Aggressiveness. Cancers (Basel). 2022; 14:4032.

[3]

Lindsey-Boltz LA, Sancar A. New biochemical approaches for the treatment of glioblastoma. J Biol Chem. 2025; 301:110748.

[4]

Pietrobono D, Giacomelli C, Marchetti L, Martini C, Trincavelli ML. High Adenosine Extracellular Levels Induce Glioblastoma Aggressive Traits Modulating the Mesenchymal Stromal Cell Secretome. Int J Mol Sci. 2020; 21:7706.

[5]

Torres A, Erices JI, Sanchez F, Ehrenfeld P, Turchi L, Virolle T, et al.Extracellular adenosine promotes cell migration/invasion of Glioblastoma Stem-like Cells through A3 Adenosine Receptor activation under hypoxia. Cancer Lett. 2019; 446:112-22.

[6]

Maity P, Ganguly S, Deb PK. Therapeutic potential of adenosine receptor modulators in cancer treatment. RSC Adv. 2025; 15:20418-45.

[7]

Franco R, Rivas-Santisteban R, Navarro G, Reyes-Resina I. Adenosine Receptor Antagonists to Combat Cancer and to Boost Anti-Cancer Chemotherapy and Immunotherapy. Cells. 2021; 10:2831.

[8]

Vazquez-Rodriguez S, Matos MJ, Santana L, Uriarte E, Borges F, Kachler S, et al.Chalcone-based derivatives as new scaffolds for hA3 adenosine receptor antagonists. J Pharm Pharmacol. 2013; 65:697-703.

[9]

Ji XD, Melman N, Jacobson KA. Interactions of flavonoids and other phytochemicals with adenosine receptors. J Med Chem. 1996; 39:781-8.

[10]

Lee HE, Jeon SJ, Ryu B, Park SJ, Ko SY, Lee Y, et al.Swertisin, a C-glucosylflavone, ameliorates scopolamine-induced memory impairment in mice with its adenosine A1 receptor antagonistic property. Behav Brain Res. 2016; 306:137-45.

[11]

Karton Y, Jiang JL, Ji XD, Melman N, Olah ME, Stiles GL, et al.Synthesis and biological activities of flavonoid derivatives as A3 adenosine receptor antagonists. J Med Chem. 1996; 39:2293-301.

[12]

Groenewald I, van Rensburg HDJ, Terre’Blanche G. Flavone and flavonol derivatives as A1/A2A receptor ligands: Structure-affinity insights. Results Chem. 2025; 16:102391.

[13]

Olson CA, Thornton JA, Adam GE, Lieberman HR. Effects of 2 adenosine antagonists, quercetin and caffeine, on vigilance and mood. J Clin Psychopharmacol. 2010; 30:573-8.

[14]

Schmidt J, Ferk P. Safety issues of compounds acting on adenosinergic signalling. J Pharm Pharmacol. 2017; 69:790-806.

[15]

Chen JF, Eltzschig HK, Fredholm BB. Adenosine receptors as drug targets--what are the challenges?. Nat Rev Drug Discov. 2013; 12:265-86.

[16]

Zhuang WB, Li YH, Shu XC, Pu YT, Wang XJ, Wang T, et al.The Classification, Molecular Structure and Biological Biosynthesis of Flavonoids, and Their Roles in Biotic and Abiotic Stresses. Molecules. 2023; 28:3599.

[17]

Shah A, Smith DL. Flavonoids in agriculture: Chemistry and roles in, biotic and abiotic stress responses, and microbial associations. Agronomy. 2020; 10:1209.

[18]

Al-Khayri JM, Sahana GR, Nagella P, Joseph BV, Alessa FM, Al-Mssallem MQ. Flavonoids as Potential Anti-Inflammatory Molecules: A Review. Molecules. 2022; 27:2901.

[19]

Pyo Y, Kwon KH, Jung YJ. Anticancer Potential of Flavonoids: Their Role in Cancer Prevention and Health Benefits. Foods. 2024; 13:2253.

[20]

Sak K. GPCRs as targets for flavonoids in cancer cells: new options for intervention. Explor Target Antitumor Ther. 2024; 5:1155-67.

[21]

Alexander SPH. Flavonoids as antagonists at A1 adenosine receptors. Phytother Res. 2006; 20:1009-12.

[22]

Santos-Buelga C. Polyphenols and Human Beings: From Epidemiology to Molecular Targets. Molecules. 2021; 26:4218.

[23]

Hasrat JA, Pieters L, Claeys M, Vlietinck A, Backer JPD, Vauquelin G. Adenosine-1 active ligands: cirsimarin, a flavone glycoside from Microtea debilis. J Nat Prod. 1997; 60:638-41.

[24]

Jacobson KA, Moro S, Manthey JA, West PL, Ji X. Interactions of flavones and other phytochemicals with adenosine receptors. Adv Exp Med Biol. 2002; 505:163-71.

[25]

Moro S, Rhee AMv, Sanders LH, Jacobson KA. Flavonoid derivatives as adenosine receptor antagonists: a comparison of the hypothetical receptor binding site based on a comparative molecular field analysis model. J Med Chem. 1998; 41:46-52.

[26]

Thilakarathna SH, Rupasinghe HPV. Flavonoid bioavailability and attempts for bioavailability enhancement. Nutrients. 2013; 5:3367-87.

[27]

Jäger AK, Saaby L. Flavonoids and the CNS. Molecules. 2011; 16:1471-85.

[28]

Li L, Guo Q, Liu Y, Lu M, Yang J, Ge Y, et al.Targeted combination therapy for glioblastoma by co-delivery of doxorubicin, YAP-siRNA and gold nanorods. J Mater Sci Technol. 2021; 63:81-90.

[29]

Alrushaid N, Khan FA, Al-Suhaimi EA, Elaissari A. Nanotechnology in Cancer Diagnosis and Treatment. Pharmaceutics. 2023; 15:1025.

[30]

Sarfraz Z, Maharaj A, Venur VA, Lathia JD, Odia Y, Ahluwalia MS. Immunotherapy in Glioblastoma: An Overview of Current Status. Clin Pharmacol. 2025; 17:185-209.

PDF (738KB)

0

Accesses

0

Citation

Detail

Sections
Recommended

/