| RESEARCH ARTICLE
|Year : 2013 | Volume
| Issue : 6 | Page : 597-602
Reversal of multidrug resistance by 5,5'-dimethoxylariciresinol-4-O-β-D-glucoside in doxorubicin-resistant human leukemia K562/DOX
Tian-Xiao Wang1, Xiao-Yan Shi1, Yue Cong1, Shi-Guang Wang2, Ying-Ying Wang1, Zhong-Qin Zhang1
1 Institute of Traditional Chinese Medicine, College of Pharmacy, Henan University, Kaifeng, Henan Province, China
2 Institute of Traditional Chinese Medicine, College of Pharmacy, Henan University; College of Huaxin, Zhengzhou, Henan Province, China
Objective: The objective of this study was to investigate the reversal effects of 5,5'-dimethoxylariciresinol-4'-O-β-D-glucoside (DMAG) extracted from traditional Chinese medicines Mahonia on multidrug resistance (MDR) of human leukemia cells to chemotherapeutic agents.
Materials and Methods: MTT(3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was performed to determine the effect of DMAG on doxorubicin sensitivity to K562/DOX cells. Propidium iodide /Hoechst 33342 double staining assay was used to investigate the effect of DMAG on doxorubicin-induced cellular apoptosis. Intracellular accumulation of doxorubicin and rhodamine 123 assay were performed to evaluate the effect of DMAG on drugs efflux activity of P-glycoprotein.
Results: DMAG significantly enhanced the doxorubicin cytotoxicity to K562/DOX cells. In the presence of 1.0 μM of DMAG, the IC 50 of doxorubicin decreased from 34.93 ± 1.37 μM to 12.51 ± 1.28 μM. DMAG of 1.0 μM significantly enhanced doxorubicin-induced cell apoptosis in K562/DOX cells and the enhancement was time-dependent. A significant increase in accumulation of doxorubicin in the presence of DMAG was observed. After treatment of the K562/DOX cells for 1 h with 15.0 μM doxorubicin alone, the fluorescence intensity was 33093.12. With the addition of 1.0 μM of DMAG, the fluorescence intensity of doxorubicin was 2.3-fold higher. A significant increase of accumulation of rhodamine 123 in the presence of DMAG was also observed. With the addition of 1.0 μM of DMAG, the fluorescence intensity was increased by 49.11% compared with rhodamine 123 alone.
Conclusion: DMAG was shown to effectively enhance chemosensitivity of resistant cells, which makes it might be a suitable candidate for potential MDR-reversing agents.
Institute of Traditional Chinese Medicine, College of Pharmacy, Henan University, Kaifeng, Henan Province
Source of Support: A grant from the Key Science and Technology Fund of Henan Province (No. 092102310159; 102300410227) in China., Conflict of Interest: None
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