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Query: UMLS:C0393754 (
HSA
)
2,996
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Boron neutron capture therapy (BNCT) requires pharmaceutical innovations and molecular-based evidence of effectiveness to become a standard cancer therapeutic in the future. Recently, in Japan, 4-borono-L-phenylalanine (BPA) was approved as a boron agent for BNCT against head and neck (H&N) cancers. H&N cancer appears to be a suitable target for BPA-BNCT, because the expression levels of L-type amino acid transporter 1 (LAT1), one of the amino acid transporters responsible for BPA uptake, are elevated in most cases of H&N cancer. However, in other types of cancer including malignant brain tumors, LAT1 is not always highly expressed. To expand the possibility of BNCT for these cases, we previously developed poly-arginine peptide (polyR)-conjugated mercaptoundecahydrododecaborate (
BSH
). PolyR confers the cell membrane permeability and tumor selectivity of
BSH
. However, the molecular determinants for the properties are not fully understood. In this present study, we have identified the cluster of differentiation 44 (CD44) protein and translational machinery proteins as a major cell surface target and intracellular targets of
BSH
-polyR, respectively. CD44, also known as a stem cell-associated maker in various types of cancer, is required for the cellular uptake of polyR-conjugated molecules. We showed that
BSH
-polyR was predominantly delivered to a CD44
High
cell population of cancer cells. Once delivered,
BSH
-polyR interacted with the translational machinery components, including the initiation factors, termination factors, and poly(A)-biding protein (
PABP
). As a proof of principle, we performed
BSH
-polyR-based BNCT against glioma stem-like cells and revealed that
BSH
-polyR successfully induced BNCT-dependent cell death specifically in CD44
High
cells. Bioinformatics analysis indicated that
BSH
-polyR would be suitable for certain types of malignant tumors. Our results shed light on the biochemical properties of
BSH
-polyR, which may further contribute to the therapeutic optimization of
BSH
-BNCT in the future.
...
PMID:In Vitro Studies to Define the Cell-Surface and Intracellular Targets of Polyarginine-Conjugated Sodium Borocaptate as a Potential Delivery Agent for Boron Neutron Capture Therapy. 3297 22
