Reversal of multidrug resistance by 5,5′-dimethoxylariciresinol-4-O-β-D-glucoside in doxorubicin-resistant human leukemia K562/DOX

• Published in: Indian journal of pharmacology Vol. 45; no. 6; pp. 597 - 602
• Main Authors: Wang, Tian-Xiao, Shi, Xiao-Yan, Cong, Yue, Wang, Shi-Guang, Wang, Ying-Ying, Zhang, Zhong-Qin
• Format: Journal Article
• Language: English
• Published: India Medknow Publications 01.11.2013; Medknow Publications & Media Pvt Ltd
• Subjects: Antibiotics, Antineoplastic - therapeutic use; Doxorubicin - therapeutic use; Drug Resistance, Multiple; Glucosides - therapeutic use; Humans; K562 Cells; Leukemia, Erythroblastic, Acute - drug therapy; Lignans - therapeutic use; leukemia; multidrug resistance; doxorubicin; 5; 5′-dimethoxylariciresinol-4′-O-β-D-glucoside; 5,5’-dimethoxylariciresinol-4’-O-β-D-glucoside
• ISSN: 0253-7613; 1998-3751
• DOI: 10.4103/0253-7613.121371

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.