An engineered microfluidic blood-brain barrier model to evaluate the anti-metastatic activity of β-boswellic acid

Saeid Vakilian, Khurshid Alam*, Juhaina Al-Kindi, Fatemeh Jamshidi-Adegani, Najeeb Ur Rehman, Rezvan Tavakoli, Khamis Al-Riyami, Anwarul Hasan, Fahad Zadjali, Rene Csuk, Ahmed Al-Harrasi, Sulaiman Al-Hashmi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
JournalBiotechnology Journal
DOIs
Publication statusAccepted/In press - 2021

Keywords

  • blood-brain barrier
  • boswellic acid
  • metastasis
  • microfluidics
  • Transwell

ASJC Scopus subject areas

  • Applied Microbiology and Biotechnology
  • Molecular Medicine

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