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:3.6.3.44 (
P-glycoprotein
)
13,344
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
To treat cancer cells overexpressing
P-glycoprotein
(
P-gp
), we propose a new concept using a nanodrug. The nanodrug was prepared from polyethyleneimine (PEI)/all-trans retinoic acid (ATRA) conjugates (
PRA
) and covered with hyaluronic acid (HA) to control the cytotoxicity of
PRA
(yielding
PRA
-H). The size distribution of
PRA
-H was narrow, with an average particle size of approximately 143 nm. Its superior stability in phosphate-buffered saline (PBS) was verified by monitoring changes in particle size and zeta potential for 24 h, which were negligible. In contrast, PEI-H (not conjugated with ATRA) exhibited a significant change in particle size and zeta potential. Although
PRA
was highly cytotoxic against HCT-8 and SNU-484 cancer cells, both of which overexpress
P-gp
, the cytotoxicity was significantly reduced by shielding with HA. The cytotoxicity of
PRA
-H was recovered by treatment with hyaluronidase (HAase), which degrades HA and is present in tumors at high concentrations. These results were confirmed by optical microscopy, fluorescence-activated cell sorting (FACs) analysis, and confocal microscopy. The cytotoxic mechanism of
PRA
was revealed as a type of necrotic lysis by FACs analysis with propidium iodide (PI) staining. Furthermore,
PRA
increased HCT-8 cell (colon cancer) permeability to doxorubicin (DOX). Therefore, we concluded that
PRA
-H is a promising new candidate for the treatment of cells with multidrug resistance (MDR) induced by overexpression of
P-gp
and cancer stem cells.
...
PMID:Polycationic nanodrug covered with hyaluronic acid for treatment of P-glycoprotein overexpressing cancer cells. 2068 38
