Abstract
Flavonoids are polyphenolic plant secondary metabolites with pleiotropic biological properties, including anti-cancer activities. These natural compounds have potential utility in glioblastoma (GBM), a malignant central nervous system tumor derived from astrocytes. Conventional GBM treatment modalities such as chemotherapy, radiation therapy, and surgical tumor resection are beneficial but limited by extensive tumor invasion and drug/radiation resistance. Therefore, dietary flavonoids—with demonstrated anti-GBM properties in preclinical research—are potential alternative therapies. This review explores the synergistic enhancement of the anti-GBM effects of conventional chemotherapeutic drugs by flavonoids. Primary studies published between 2011 and 2021 on flavonoid–chemotherapeutic synergy in GBM were obtained from PubMed. These studies demonstrate that flavonoids such as chrysin, epigallocatechin-3-gallate (EGCG), formononetin, hispidulin, icariin, quercetin, rutin, and silibinin synergistically enhance the effects of canonical chemotherapeutics. These beneficial effects are mediated by the modulation of intracellular signaling mechanisms related to apoptosis, proliferation, autophagy, motility, and chemoresistance. In this light, flavonoids hold promise in improving current therapeutic strategies and ultimately overcoming GBM drug resistance. However, despite positive preclinical results, further investigations are necessary before the commencement of clinical trials. Key considerations include the bioavailability, blood–brain barrier (BBB) permeability, and safety of flavonoids; optimal dosages of flavonoids and chemotherapeutics; drug delivery platforms; and the potential for adverse interactions.
Highlights
Bioactive flavonoids occur in fruits, vegetables, and other natural plant products and Bioactive flavonoids occur in fruits, vegetables, and other are unified by a three-ring structural backbone that includes twonatural phenylplant ringsproducts and one and are unified by a three-ring structural backbone that includes two phenyl rings and one central heterocyclic ring
C/EBP homologous protein (CHOP) and downregulating glucose-regulated protein 78 (GRP78) and inducing endoplasmic reticulum (ER) stress, which contributes to apoptosis [32]
Intracellular Ca2+ enters mitochondria via the mitochondrial Ca2+ uniporter (MCU); increased mitochondrial calcium concentrations ([Ca2+ ]m ) upregulate the generation of reactive oxygen species (ROS), which in turn contribute to caspase-induced apoptosis [43]
Summary
Glioblastoma (GBM) is an astrocyte-derived solid tumor of the brain or spinal cord that occurs at an overall rate of 3.19 cases per 100,000 individuals in the United States. Astatic inhibition, and apoptotic induction [12,13] Based on these well-evidenced onFlavonoids exert anti-cancer effects through chemosensitization, metabolic modulation, costatic activities, flavonoids have great potential in modulating GBM cell responses to metastatic inhibition, and apoptotic induction [12,13]. Based on these well-evidenced anti-cancer drugs by overcoming their therapeutic resistance. This reviewThe aims to complement anti-cancer documented drugs by overcoming theirresearch therapeutic efficacy of flavonoids previous research focusing oninthe synergistic efficacy of This flavonoids conventional in GBM is wellby documented preclinical research [14]. Previous research by focusing on the synergistic efficacy of flavonoids and conventional chemotherapeutics in GBM therapy
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