BNCT Displays Cytotoxic Effect on Malignant Meningioma Via the Induction of DNA Damage
DOI:
https://doi.org/10.48048/tis.2025.10511Keywords:
BNCT, DNA damage, Malignant meningiomas, L-Type amino acid transporter 1Abstract
Malignant meningiomas are an aggressive cancer with high recurrence and poor prognosis. It is difficult to treat via surgical resection and radiotherapy, especially recurrent meningiomas. Boron neutron capture therapy (BNCT) is a targeted radiotherapy that can selectively kill malignant tumor cells with increased uptake of p-10B-para-boronophenylalanine (BPA) via up-regulation of L-Type Amino Acid Transporter 1 (LAT1). BNCT has been used in clinical studies to treat malignant meningiomas. However, it has never been reported on the basic study of BNCT and the mechanism of BNCT-mediated cell death in the meningiomas. The results of the present study demonstrated that LAT1 was a major LAT isoform in meningiomas. High mRNA expression of LAT1 was observed in both malignant meningioma cell lines and primary benign meningioma cells. The intracellular retention of 10B was increased in dose- and time-dependent manners. The cell viability of HKBMM cells after boron neutron irradiation for 30 min was decreased as 4-borono-L-phenylalanine-fructose (L-BPA-fr) concentration increased. Next, the effect of BNCT on DNA damage was performed via the expression of phosphorylated H2AX (γH2AX). The increase in γH2AX foci per nucleus, brighter and larger of foci were associated with the increase of intracellular 10B concentrations and radiation dose. Taken together, our findings suggest that the efficacy of BNCT on DNA damage and cell viability depends on the intracellular retention of 10B and radiation dosage.
HIGHLIGHTS
- LAT1 is highly expressed in meningiomas.
- L-BPA-fr mediated ¹⁰B uptake increases in a dose- and time-dependent manner.
- BNCT significantly decreases cell viability in malignant meningioma cells.
- BNCT induces γH2AX foci formation associated with DNA double-strand breaks.
- The efficacy of BNCT depends on intracellular ¹⁰B retention and neutron radiation dose.
GRAPHICAL ABSTRACT
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