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Reversal of multidrug resistance by icaritin in doxorubicin-resistant human osteosarcoma cells.
Chin J Nat Med. 2018 Jan; 16(1):20-28.CJ

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-1. 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.

Authors+Show Affiliations

State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China. Electronic address: cpu_lykong@126.com.State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China. Electronic address: dorothy19802003@gmail.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29425587

Citation

Wang, Zhen-Dong, et al. "Reversal of Multidrug Resistance By Icaritin in Doxorubicin-resistant Human Osteosarcoma Cells." Chinese Journal of Natural Medicines, vol. 16, no. 1, 2018, pp. 20-28.
Wang ZD, Wang RZ, Xia YZ, et al. Reversal of multidrug resistance by icaritin in doxorubicin-resistant human osteosarcoma cells. Chin J Nat Med. 2018;16(1):20-28.
Wang, Z. D., Wang, R. Z., Xia, Y. Z., Kong, L. Y., & Yang, L. (2018). Reversal of multidrug resistance by icaritin in doxorubicin-resistant human osteosarcoma cells. Chinese Journal of Natural Medicines, 16(1), 20-28. https://doi.org/10.1016/S1875-5364(18)30026-8
Wang ZD, et al. Reversal of Multidrug Resistance By Icaritin in Doxorubicin-resistant Human Osteosarcoma Cells. Chin J Nat Med. 2018;16(1):20-28. PubMed PMID: 29425587.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reversal of multidrug resistance by icaritin in doxorubicin-resistant human osteosarcoma cells. AU - Wang,Zhen-Dong, AU - Wang,Rui-Zhi, AU - Xia,Yuan-Zheng, AU - Kong,Ling-Yi, AU - Yang,Lei, PY - 2017/05/25/received PY - 2018/2/10/entrez PY - 2018/2/10/pubmed PY - 2018/7/27/medline KW - Icaritin KW - MDR1 KW - MRP1 KW - Multidrug resistance KW - Osteosarcoma SP - 20 EP - 28 JF - Chinese journal of natural medicines JO - Chin J Nat Med VL - 16 IS - 1 N2 - 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-1. 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. SN - 1875-5364 UR - https://www.unboundmedicine.com/medline/citation/29425587/Reversal_of_multidrug_resistance_by_icaritin_in_doxorubicin_resistant_human_osteosarcoma_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1875-5364(18)30026-8 DB - PRIME DP - Unbound Medicine ER -