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

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 beta-boswellic acid (beta-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 beta-BA deteriorates MDA-MB-231 cells, while beta-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 beta-BA. Vimentin expression in HUVECs, evaluated using western blot, confirmed superior barrier integrity in the presence of beta-BA. The obtained results were confirmed using an invasion study with a cell tracker and a scanning electron microscope. beta-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 beta-BA-mediated metastasis inhibition was significantly higher than that mediated by Cis. Conclusions and Implications: In summary, the current study proved the antimetastatic potential of g-BA in both static and dynamic BBB models.

Automated summary

This study demonstrated the antimetastatic potential of beta-boswellic acid in inhibiting the metastasis of MDA-MB-231 cells through the blood-brain barrier (BBB) using different in vitro models. The results showed that beta-BA had no toxic effects on other cells and maintained sustainable barrier integrity, significantly inhibiting metastasis.