Polyoxypregnanes as safe, potent, and specific ABCB1-inhibitory pro-drugs to overcome multidrug resistance in cancer chemotherapy
10.1016/j.apsb.2020.12.021
- Author:
Xu WU
1
;
Chun YIN
1
;
Jiang MA
1
;
Stella CHAI
1
;
Chunyuan ZHANG
1
;
Sheng YAO
2
;
Onat KADIOGLU
3
;
Thomas EFFERTH
3
;
Yang YE
2
;
Kenneth Kin-Wah TO
4
;
Ge LIN
1
Author Information
1. School of Biomedical Sciences, Faculty of Medicine, the Chinese University of Hong Kong, Hong Kong 999077, China.
2. Joint Research Laboratory of Promoting Globalization of Traditional Chinese Medicines between the Chinese University of Hong Kong and Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Hong Kong 999077, China.
3. Department of Pharmaceutical Biology, Johannes Gutenberg University, Mainz 55099, Germany.
4. School of Pharmacy, Faculty of Medicine, the Chinese University of Hong Kong, Hong Kong 999077, China.
- Publication Type:Journal Article
- Keywords:
ABC, ATP-binding cassette;
ABCB1;
ABCB1, ATP binding cassette subfamily B member 1;
ABCC1, ATP binding cassette subfamily C member 1;
ABCG2, ATP binding cassette subfamily G member 2;
ATF3, activating transcription factor 3;
AUC0–∞, area under plasma concentration vs. time curve;
BBB, blood–brain barrier;
BHI, brain heart infusion;
CL, clearance;
CYP, cytochrome P450 isozyme;
Cmax, peak concentration;
Combination chemotherapy;
Dox, doxorubicin;
ECL, electrochemiluminescence;
EVOM, epithelial tissue voltohmmeter;
F, bioavailability;
FBS, fetal bovine serum;
GAPDH, glyceraldehyde-3-phosphate dehydrogenase;
H&E, hematoxylin and eosin;
HBSS, Hankʹs balanced salt solution;
IC50, half maximal inhibitory concentration;
LBE, lowest binding energy;
LC–MS, liquid chromatography coupled with mass spectrometry;
M. tenacissima, Marsdenia tenacissima;
MDR, multidrug resistance;
MDR1a, multidrug resistance protein 1a;
MRT, mean residence time;
Marsdenia tenacissima;
Multidrug resistance;
N.A., not applicable;
N.D., not detected;
NADPH, reduced nicotinamide adenine dinucleotide phosphate;
NMPA, National Medical Products Administration;
PBS, phosphate buffer saline;
PCR, polymerase chain reaction;
PE, phycoerythrin;
PI, propidium iodide;
POP, polyoxypregnane;
PXR, pregnane X receptor;
Papp, apparent permeability;
Polyoxypregnane;
SD, standard derivation;
SDS-PAGE, sodium dodecyl sulfate-polyacrylamide gel electrophoresis;
TEER, transepithelial electrical resistance;
Tmax, time for peak concentration;
UIC-2, mouse monoclonal ABCB1 antibody;
Vd, volume of distribution;
qPCR, quantitative PCR;
t1/2, elimination half-life
- From:
Acta Pharmaceutica Sinica B
2021;11(7):1885-1902
- CountryChina
- Language:English
-
Abstract:
Multidrug resistance (MDR) mediated by ATP binding cassette subfamily B member 1 (ABCB1) is significantly hindering effective cancer chemotherapy. However, currently, no ABCB1-inhibitory drugs have been approved to treat MDR cancer clinically, mainly due to the inhibitor specificity, toxicity, and drug interactions. Here, we reported that three polyoxypregnanes (POPs) as the most abundant constituents of
