TY - JOUR
T1 - An engineered microfluidic blood-brain barrier model to evaluate the anti-metastatic activity of β-boswellic acid
AU - Vakilian, Saeid
AU - Alam, Khurshid
AU - Al-Kindi, Juhaina
AU - Jamshidi-Adegani, Fatemeh
AU - Rehman, Najeeb Ur
AU - Tavakoli, Rezvan
AU - Al-Riyami, Khamis
AU - Hasan, Anwarul
AU - Zadjali, Fahad
AU - Csuk, Rene
AU - Al-Harrasi, Ahmed
AU - Al-Hashmi, Sulaiman
N1 - Funding Information:
This research was funded by the GCC co‐funding, grant number CL/SQU‐GCC/17/03, and The Research Council external grant number BFP/RGP/HSS/18/024, 2019. The authors acknowledge the financial and technical support provided by the University of Nizwa and Sultan Qaboos University. In addition, the authors gratefully acknowledge Mr Saleh Al‐Amri for the collection of oleo‐gum resins of () from the Dhofar region (Oman). Boswellia sacra B. sacra
Publisher Copyright:
© 2021 Wiley-VCH GmbH
PY - 2021/10
Y1 - 2021/10
N2 - 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: 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: 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: In summary, the current study proved the anti-metastatic potential of β-BA in both static and dynamic BBB models. Graphical Abstract and Lay Summary: (Figure presented.) 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. In summary, the current study proved the anti-metastatic potential of β-BA in both static and dynamic BBB models.
AB - 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: 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: 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: In summary, the current study proved the anti-metastatic potential of β-BA in both static and dynamic BBB models. Graphical Abstract and Lay Summary: (Figure presented.) 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. In summary, the current study proved the anti-metastatic potential of β-BA in both static and dynamic BBB models.
KW - blood-brain barrier
KW - boswellic acid
KW - metastasis
KW - microfluidics
KW - Transwell
KW - Human Umbilical Vein Endothelial Cells
KW - Humans
KW - Triterpenes/pharmacology
KW - Microfluidics
KW - Blood-Brain Barrier
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UR - http://www.scopus.com/inward/citedby.url?scp=85112753324&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/663ec4cf-b935-3cd7-9048-fe5a4f421e85/
U2 - 10.1002/biot.202100044
DO - 10.1002/biot.202100044
M3 - Article
C2 - 34313388
AN - SCOPUS:85112753324
SN - 1860-6768
VL - 16
JO - Biotechnology Journal
JF - Biotechnology Journal
IS - 10
M1 - 2100044
ER -
