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Natural Flavonoid Apigenin, an Effective Agent Against Nervous System Cancers

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Abstract

Cancer is a serious public health concern worldwide, and nervous system (NS) cancers are among the most life-threatening malignancies. Efforts have been devoted to introduce natural anticancer agents with minimal side effects. Apigenin is an edible flavonoid that is abundantly found in many vegetables and fruits. Various pharmaceutical activities, including anti-inflammatory, antioxidative, antimicrobial, and anticancer effects have been reported for apigenin. This review provides insights into the therapeutic effects of apigenin and flavonoids with similar structure on glioblastoma and neuroblastoma. Current evidence indicates that apigenin has the unique ability to cross the blood-brain barrier, and its antioxidative, anti-inflammatory, neurogenic, and neuroprotective effects have made this flavonoid a great option for the treatment of neurodegenerative disorders. Meanwhile, apigenin has low toxicity on normal neuronal cells, while induces cytotoxicity on NS cancer cells via triggering several signal pathways and molecular targets. Anticancer effects of apigenin have been contributed to various mechanisms such as induction of cell cycle arrest and apoptosis, and inhibition of migration, invasion, and angiogenesis. Although apigenin is a promising pharmaceutical agent, its low bioavailability is an important issue that must be solved before introducing to clinic. Recently, nano-delivery of apigenin by liposomes and poly lactic-co-glycolide nanoparticles has greatly improved functionality of this agent. Hence, investigating pharmaceutical effects of apigenin-loaded nanocarriers on NS cancer cell lines and animal models is recommended for future studies.

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Abbreviations

AKT:

Ak strain transforming

AMPK:

AMP-activated protein kinase

BDNF:

Brain-derived neurotrophic factor

CDK-1:

Cyclin-dependent kinase 1

c-FLIP:

Cellular FADD-like IL-1β-converting enzyme-inhibitory protein

c-Met:

Mesenchymal-epithelial transition factor

EGFR:

Epidermal growth factor receptor

ERK:

Extracellular signal-regulated kinase

GDNF:

Glial-derived neurotrophic factor

GFAP:

Glial fibrillary acidic protein

GLUT:

Glucose transporters

GPx:

Glutathione peroxidase

hTERT:

Human telomerase reverse transcriptase

HIF-1α:

Hypoxia-inducible factor-1 α

IL:

Interleukin

JAK:

Janus kinase

KLF4:

Krüpple-like factor 4

LPS:

Lipopolysaccharide

MAPK:

Mitogen-activated protein kinase

MCL1:

Myeloid cell leukemia 1

MMPs:

Matrix metalloproteinases

mTOR:

Mammalian target of rapamycin

NK:

Natural killer

NF-κB:

Nuclear factor kappa B

Nrf2:

Nuclear factor erythroid 2–related factor 2

NS:

Nervous system

PARP:

Poly ADP-ribose polymerase

PCNA:

Proliferating cell nuclear antigen

PI3K:

Phosphatidylinositol-3 kinase

PKM2:

Pyruvate kinase isozyme type M2

PLGA:

Poly lactic-co-glycolide

ROS:

Reactive oxygen species

STAT:

Signal transducers and activators of transcription

TGFβ:

Transforming growth factor-beta

TNF-α:

Tumor necrosis factor alpha

VEGF:

Vascular endothelial growth factor

Wnt:

Wingless-related integration site

XIAP:

X-linked inhibitor of apoptosis protein

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Acknowledgements

The authors would like to thank Mrs. F. Hosseini for her assistance.

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This work was supported by Ferdowsi University of Mashhad, Iran.

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  1. Novel Diagnostics and Therapeutics Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran

    Mohammad-Sadegh Lotfi & Fatemeh B. Rassouli

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  1. Mohammad-Sadegh Lotfi
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Mohammad-Saegh Lotfi was responsible for conceptualization and investigation, and Fatemeh B. Rassouli supervised and edited the manuscript.

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Correspondence to Fatemeh B. Rassouli.

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Lotfi, MS., Rassouli, F.B. Natural Flavonoid Apigenin, an Effective Agent Against Nervous System Cancers. Mol Neurobiol (2024). https://doi.org/10.1007/s12035-024-03917-y

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