posted on 2018-11-26, 00:00authored byTianyu He, Sridar V. Chittur, Rabi A. Musah
Carboranes have been
extensively investigated as potential drugs
for the treatment of malignant human brain tumors by boron neutron
capture therapy (BNCT). This noninvasive treatment modality utilizes
compounds containing the nonradioactive isotope 10B which
has a high propensity to capture slow neutrons. In response, it emits
high energy α-particles that kill the cell. We have successfully
synthesized a boron delivery agent by installing a boron-rich m-carborane within the amino acid cysteine. Rapid uptake
of this compound into U87 glioblastoma cells within 5 min of exposure
was observed, and fluorescence microscopy studies showed that it was
retained intracellularly after 48 h. In the absence of thermal neutrons,
a cytostatic effect in U87 cells was observed at exposures ranging
from 1 μM to 1 mM relative to the control, while no change was
observed at 1–0.01 μM. Microarray studies unveiled a
wide range of unique changes in the gene expression profile of the
U87 cells, particularly for the genes associated with cell cycle,
which were observed to be greatly suppressed after treatment with
the compound. These results were validated by qPCR studies. Although
the compound was designed for BNCT, its distinctive impacts on gene
regulation reveal that it and other carborane-containing cluster molecules
may exert unique heretofore unknown effects on the transcriptome,
even in the absence of applied radiation.