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Caffeine Effect on HIFs/VEGF Pathway in Human Glioblastoma Cells Exposed to Hypoxia.
Anticancer Agents Med Chem. 2018; 18(10):1432-1439.AA

Abstract

BACKGROUND

Caffeine represents the most used psychoactive drug in the world acting through different mechanisms of action and on several molecular targets. It exerts an anti-cancer role in glioblastoma multiforme (GBM). This neoplasia is characterized by extensive hypoxic foci triggering hypoxia-inducible factors (HIFs) expression. Among these factors, HIF-1α performs a crucial role in the induction of vascular endothelium growth factor (VEGF), a key player in angiogenesis and cell migration.

METHODS

In this work, we have investigated whether caffeine counteracts GBM progression by modulating hypoxic event. Moreover, we analyzed the activation of phosphoinositide three kinase (PI3K)/Akt and mammalian mitogen activated protein kinase/Erk kinase (MAPK/ERK) signaling cascades.

RESULTS

Our results have indicated that this psychostimulant drug significantly reduced HIF-1α and VEGF expression in GBM cells exposed to hypoxia. This effect is mediated through inhibition of PI3K/Akt and MAPK/ERK signaling pathways both implied in HIFs regulation.

CONCLUSION

The present data give new insight into antitumor activity of caffeine during GBM progression.

Links

Publisher Full Text (DOI)

Authors+Show Affiliations

Maugeri G
Section of Human Anatomy and Histology, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
D'Amico AG
Department of Human Science and Promotion of Quality of Life, the San Raffaele Open University of Rome, Rome, Italy.
Rasà DM
Section of Human Anatomy and Histology, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
Saccone S
Section of Animal Biology, Department of Biological, Geological and Environmental Sciences, University of Catania, Catania, Italy.
Federico C
Section of Animal Biology, Department of Biological, Geological and Environmental Sciences, University of Catania, Catania, Italy.
Magro G
Department of Medical and Surgical Sciences and Advanced Technologies, Anatomic Pathology Section, School of Medicine, University of Catania, Catania, Italy.
Cavallaro S
Institute of Neurological Sciences, National Research Council, Catania, Italy.
D'Agata V
Section of Human Anatomy and Histology, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.

MeSH

Antineoplastic AgentsBasic Helix-Loop-Helix Transcription FactorsCaffeineCell Line, TumorCell ProliferationDose-Response Relationship, DrugDrug Screening Assays, AntitumorGlioblastomaHumansHypoxiaMolecular ConformationProtein Kinase InhibitorsStructure-Activity RelationshipVascular Endothelial Growth Factors

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29424319

Citation

Maugeri, Grazia, et al. "Caffeine Effect On HIFs/VEGF Pathway in Human Glioblastoma Cells Exposed to Hypoxia." Anti-cancer Agents in Medicinal Chemistry, vol. 18, no. 10, 2018, pp. 1432-1439.
Maugeri G, D'Amico AG, Rasà DM, et al. Caffeine Effect on HIFs/VEGF Pathway in Human Glioblastoma Cells Exposed to Hypoxia. Anticancer Agents Med Chem. 2018;18(10):1432-1439.
Maugeri, G., D'Amico, A. G., Rasà, D. M., Saccone, S., Federico, C., Magro, G., Cavallaro, S., & D'Agata, V. (2018). Caffeine Effect on HIFs/VEGF Pathway in Human Glioblastoma Cells Exposed to Hypoxia. Anti-cancer Agents in Medicinal Chemistry, 18(10), 1432-1439. https://doi.org/10.2174/1871520618666180209151750
Maugeri G, et al. Caffeine Effect On HIFs/VEGF Pathway in Human Glioblastoma Cells Exposed to Hypoxia. Anticancer Agents Med Chem. 2018;18(10):1432-1439. PubMed PMID: 29424319.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Caffeine Effect on HIFs/VEGF Pathway in Human Glioblastoma Cells Exposed to Hypoxia. AU - Maugeri,Grazia, AU - D'Amico,Agata G, AU - Rasà,Daniela M, AU - Saccone,Salvatore, AU - Federico,Concetta, AU - Magro,Gaetano, AU - Cavallaro,Sebastiano, AU - D'Agata,Velia, PY - 2017/08/18/received PY - 2018/01/18/revised PY - 2018/01/30/accepted PY - 2018/2/10/pubmed PY - 2019/8/6/medline PY - 2018/2/10/entrez KW - Caffeine KW - MAPK/ERK KW - PI3K/Akt KW - glioblastoma multiforme KW - hypoxia-inducible factors KW - vascular endothelium growth factor. SP - 1432 EP - 1439 JF - Anti-cancer agents in medicinal chemistry JO - Anticancer Agents Med Chem VL - 18 IS - 10 N2 - BACKGROUND: Caffeine represents the most used psychoactive drug in the world acting through different mechanisms of action and on several molecular targets. It exerts an anti-cancer role in glioblastoma multiforme (GBM). This neoplasia is characterized by extensive hypoxic foci triggering hypoxia-inducible factors (HIFs) expression. Among these factors, HIF-1α performs a crucial role in the induction of vascular endothelium growth factor (VEGF), a key player in angiogenesis and cell migration. METHODS: In this work, we have investigated whether caffeine counteracts GBM progression by modulating hypoxic event. Moreover, we analyzed the activation of phosphoinositide three kinase (PI3K)/Akt and mammalian mitogen activated protein kinase/Erk kinase (MAPK/ERK) signaling cascades. RESULTS: Our results have indicated that this psychostimulant drug significantly reduced HIF-1α and VEGF expression in GBM cells exposed to hypoxia. This effect is mediated through inhibition of PI3K/Akt and MAPK/ERK signaling pathways both implied in HIFs regulation. CONCLUSION: The present data give new insight into antitumor activity of caffeine during GBM progression. SN - 1875-5992 UR - https://www.unboundmedicine.com/medline/citation/29424319/Caffeine_Effect_on_HIFs/VEGF_Pathway_in_Human_Glioblastoma_Cells_Exposed_to_Hypoxia_ DB - PRIME DP - Unbound Medicine ER -
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