Reversal of multidrug resistance by icaritin in doxorubicin-resistant human osteosarcoma cells.
10.1016/S1875-5364(18)30026-8
- Author:
Zhen-Dong WANG
1
;
Rui-Zhi WANG
1
;
Yuan-Zheng XIA
1
;
Ling-Yi KONG
2
;
Lei YANG
3
Author Information
1. State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
2. State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China. Electronic address: cpu_lykong@126.com.
3. State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China. Electronic address: dorothy19802003@gmail.com.
- Publication Type:Journal Article
- Keywords:
Icaritin;
MDR1;
MRP1;
Multidrug resistance;
Osteosarcoma
- MeSH:
ATP Binding Cassette Transporter, Subfamily B;
drug effects;
genetics;
metabolism;
Antineoplastic Agents;
pharmacology;
Apoptosis;
drug effects;
Cell Line, Tumor;
Cell Survival;
drug effects;
Dose-Response Relationship, Drug;
Doxorubicin;
metabolism;
pharmacology;
toxicity;
Drug Resistance, Multiple;
drug effects;
Drug Resistance, Neoplasm;
drug effects;
Flavonoids;
pharmacology;
Gene Expression Regulation, Neoplastic;
drug effects;
Humans;
Multidrug Resistance-Associated Proteins;
drug effects;
genetics;
metabolism;
Osteosarcoma;
drug therapy;
metabolism;
pathology;
Phosphorylation;
drug effects;
Rhodamine 123;
metabolism;
STAT3 Transcription Factor;
antagonists & inhibitors;
metabolism;
Triterpenes;
pharmacology
- From:
Chinese Journal of Natural Medicines (English Ed.)
2018;16(1):20-28
- CountryChina
- Language:English
-
Abstract:
Multidrug resistance (MDR) is one of the major obstacles in cancer chemotherapy. Our previous study has shown that icariin could reverse MDR in MG-63 doxorubicin-resistant (MG-63/DOX) cells. It is reported that icariin is usually metabolized to icariside II and icaritin. Herein, we investigated the effects of icariin, icariside II, and icaritin (ICT) on reversing MDR in MG-63/DOX cells. Among these compounds, ICT exhibited strongest effect and showed no obvious cytotoxicity effect on both MG-63 and MG-63/DOX cells ranging from 1 to 10 μmol·L. Furthermore, ICT increased accumulation of rhodamine 123 and 6-carboxyfluorescein diacetate and enhanced DOX-induced apoptosis in MG-63/DOX cells in a dose-dependent manner. Further studies demonstrated that ICT decreased the mRNA and protein levels of multidrug resistance protein 1 (MDR1) and multidrug resistance-associated protein 1 (MRP1). We also verified that blockade of STAT3 phosphorylation was involved in the reversal effect of multidrug resistance in MG-63/DOX cells. Taken together, these results indicated that ICT may be a potential candidate in chemotherapy for osteosarcoma.
