An engineered microfluidic blood-brain barrier model to evaluate the anti-metastatic activity of β-boswellic acid.
Transwell
blood-brain barrier
boswellic acid
metastasis
microfluidics
Journal
Biotechnology journal
ISSN: 1860-7314
Titre abrégé: Biotechnol J
Pays: Germany
ID NLM: 101265833
Informations de publication
Date de publication:
Oct 2021
Oct 2021
Historique:
revised:
11
07
2021
received:
24
01
2021
accepted:
12
07
2021
pubmed:
28
7
2021
medline:
13
10
2021
entrez:
27
7
2021
Statut:
ppublish
Résumé
The development of anti-cancer drugs with the ability to inhibit brain metastasis through the blood-brain barrier (BBB) is substantially limited due to the lack of reliable in vitro models. In this study, the Geltrex-based Transwell and microfluidic BBB models were applied to screen the effect of β-boswellic acid (β-BA) on the metastasis of MDA-MB-231 cells through the BBB in static and dynamic conditions, respectively. The toxicity assay revealed that β-BA deteriorates MDA-MB-231 cells, while β-BA had no detectable toxic effects on human umbilical vein endothelial cells (HUVECs) and astrocytes. Trans-endothelial electrical resistance evaluation showed sustainable barrier integrity upon treatment with β-BA. Vimentin expression in HUVECs, evaluated using western blot, confirmed superior barrier integrity in the presence of β-BA. The obtained results were confirmed using an invasion study with a cell tracker and a scanning electron microscope. β-BA significantly inhibited metastasis by 85%, while cisplatin (Cis), a positive control, inhibited cancer cell migration by 12% under static conditions. Upon applying a dynamic BBB model, it was revealed that β-BA-mediated metastasis inhibition was significantly higher than that mediated by Cis. In summary, the current study proved the anti-metastatic potential of β-BA in both static and dynamic BBB models.
Sections du résumé
BACKGROUND
BACKGROUND
The development of anti-cancer drugs with the ability to inhibit brain metastasis through the blood-brain barrier (BBB) is substantially limited due to the lack of reliable in vitro models.
MAIN METHODS
METHODS
In this study, the Geltrex-based Transwell and microfluidic BBB models were applied to screen the effect of β-boswellic acid (β-BA) on the metastasis of MDA-MB-231 cells through the BBB in static and dynamic conditions, respectively.
MAJOR RESULTS
RESULTS
The toxicity assay revealed that β-BA deteriorates MDA-MB-231 cells, while β-BA had no detectable toxic effects on human umbilical vein endothelial cells (HUVECs) and astrocytes. Trans-endothelial electrical resistance evaluation showed sustainable barrier integrity upon treatment with β-BA. Vimentin expression in HUVECs, evaluated using western blot, confirmed superior barrier integrity in the presence of β-BA. The obtained results were confirmed using an invasion study with a cell tracker and a scanning electron microscope. β-BA significantly inhibited metastasis by 85%, while cisplatin (Cis), a positive control, inhibited cancer cell migration by 12% under static conditions. Upon applying a dynamic BBB model, it was revealed that β-BA-mediated metastasis inhibition was significantly higher than that mediated by Cis.
CONCLUSIONS AND IMPLICATIONS
CONCLUSIONS
In summary, the current study proved the anti-metastatic potential of β-BA in both static and dynamic BBB models.
Identifiants
pubmed: 34313388
doi: 10.1002/biot.202100044
doi:
Substances chimiques
Triterpenes
0
boswellic acid
631-69-6
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2100044Informations de copyright
© 2021 Wiley-VCH GmbH.
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