Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.16.2 (
PCP
)
3,761
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The potent
N
-methyl-d-aspartate (NMDA) receptor antagonists
1
-
3
have been demonstrated to show antiproliferative and cytotoxic effects in
MCF
-7 and SKBR3 breast cancer cell lines. To improve the knowledge about the role played by the NMDA receptor in the antitumor activity of these compounds, the enantiomers of
1
were prepared and evaluated for their affinity for the phencyclidine (
PCP
) site of the NMDA receptor and for their cytotoxic effect in
MCF
-7 and SKBR3 cell lines, both expressing the NMDA receptor. The (
S
)-
1
enantiomer, showing negligible affinity for the
PCP
site, exhibited antiproliferative activity higher than that of (
R
)-
1
, which instead bound the
PCP
site. The downregulation of NMDA GluN1 expression resulted in a decreased (
S
)-
1
-induced cytotoxicity and apoptotic cell death, unequivocally demonstrating the involvement of the NMDA receptor in the antitumor effect of this compound. Due to its interesting biological profile, (
S
)-
1
represents a lead compound to develop novel antitumor agents for breast cancer treatment.
...
PMID:Role of the NMDA Receptor in the Antitumor Activity of Chiral 1,4-Dioxane Ligands in MCF-7 and SKBR3 Breast Cancer Cells. 3099 88
Multidrug resistance is one of the main causes leading to failure of chemotherapy. Therefore, the rational design of targeting drug systems to reverse multidrug resistance is becoming an important strategy for cancer therapy. Herein, we present a novel copolymer-based nanoparticle that was size changeable and could realize the goal of precise drug controlled release under acidic conditions, and could overcome the multidrug resistance in breast cancer cells. This
PCP
/uPA nanosystem was formed through the crosslinking between chitosan (CS) and poly(N-isopropylacrylamide) (PNIPAM), followed by surface decoration with polyethylene glycol (mPEG) and a breast cancer targeting peptide uPA, which was then used to encapsulate metal complexes (RuPOP and Fe(PiP)
3
) to solve their bottleneck of low solubility and stability under physiological conditions. These multifunctional nanosystems (
PCP
-Ru/uPA and
PCP
-Fe/uPA) exhibited remarkable anticancer activity and could overcome the poor stability and low solubility of RuPOP and Fe(PiP)
3
. Noticeably,
PCP
-Ru/uPA reversed the multidrug resistance of drug-resistant
MCF
-7 (
MCF
-7R) human breast cancer cells by enhancing the cellular uptake of RuPOP by
MCF
-7R cells and inhibiting the expression of ABC family proteins. Furthermore, when
PCP
-Ru/uPA was at pH 5.3 with lysozyme, the release amount of RuPOP is the largest compared with pH at 5.3 or 7.4, and the release rate of RuPOP reached 75% at 48 h. In other words, the nanosystem with a pH-responsive effect swelled in an acidic environment and released free RuPOP in the lysosome of cancer cells efficiently, which triggered ROS up-regulation and induced apoptosis in
MCF
-7R cells. Taken together, this study presents a novel size changeable nanosystem for precise drug controlled release and efficient overcoming of cancer multidrug resistance.
...
PMID:Size changeable nanosystems for precise drug controlled release and efficient overcoming of cancer multidrug resistance. 3226 72
