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Reversal effect of isotetrandrine, an isoquinoline alkaloid extracted from Caulis Mahoniae, on P-glycoprotein-mediated doxorubicin-resistance in human breast cancer (MCF-7/DOX) cells.
Yao Xue Xue Bao. 2008 May; 43(5):461-6.YX

Abstract

This study investigated the reversal effect of isotetrandrine, an isoquinoline alkaloid extracted from Caulis mahoniae, on P-glycoprotein-mediated multidrug resistance in human breast cancer doxorubicin-resistant (MCF-7/DOX) cells. RT-PCR assay and immunity histochemistry assay were used to determine the expression level of mdrl gene and P-gp in MCF-7/DOX cells to elucidate resistant character of MCF-7/DOX cells. The activity of isotetrandine to enhance doxorubicin cytotoxicity was tested using MTT (3-(4, 5-dimethyhthiazol)-2,5 -diphenyltetrazolium bromide) assay and was evaluated by the reversal fold (RF) values. Intracellular accumulation of doxorubicin was assessed by the determination of doxorubicin-associated fluorescence intensity. Effect of isotetrandrine on the expression level of P-gp in MCF-7/DOX cells was then determined by immunity histochemistry assay. The ability of isotetrandrine to inhibit P-gp function was evaluated by detecting the accumulation and efflux of rhodamine 123 (Rh123) with flow cytometry (FCM). Verapamil was employed as a comparative agent in whole experiment. The results indicated that MCF-7/DOX cells had phenotype of MDR and that the positive expression of P-gp was their resistant character. 10 microg x mL(-1) isotetrandrine could distinctly enhance cytotoxicity of DOX in MCF-7/DOX cells and reversal fold (RF) was significantly higher than that of verapamil (P < 0.05), but it hardly affected cytotoxicity of DOX in MCF-7 cells and the expression level of P-gp in MCF-7/DOX cells. The ability of isotetrandrine to inhibit P-gp function was reversible, because incubation of MCF-7/DOX cells with isotetrandrine caused a marked increase in uptake and a notable decrease in efflux of Rh123 and a marked increase of intracellular DOX concentrations. In conclusion, isotetrandrine exhibited potent effect on the reversal of P-gp-mediated MDR in vitro, suggesting that it might become a candidate of effective MDR reversing agent in cancer chemotherapy.

Authors+Show Affiliations

Institute of Pharmacy, Henan University, Kaifeng 475004, China. wtx1975@henu.edu.cnNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18717331

Citation

Wang, Tian-Xiao, and Xiao-Hong Yang. "Reversal Effect of Isotetrandrine, an Isoquinoline Alkaloid Extracted From Caulis Mahoniae, On P-glycoprotein-mediated Doxorubicin-resistance in Human Breast Cancer (MCF-7/DOX) Cells." Yao Xue Xue Bao = Acta Pharmaceutica Sinica, vol. 43, no. 5, 2008, pp. 461-6.
Wang TX, Yang XH. Reversal effect of isotetrandrine, an isoquinoline alkaloid extracted from Caulis Mahoniae, on P-glycoprotein-mediated doxorubicin-resistance in human breast cancer (MCF-7/DOX) cells. Yao Xue Xue Bao. 2008;43(5):461-6.
Wang, T. X., & Yang, X. H. (2008). Reversal effect of isotetrandrine, an isoquinoline alkaloid extracted from Caulis Mahoniae, on P-glycoprotein-mediated doxorubicin-resistance in human breast cancer (MCF-7/DOX) cells. Yao Xue Xue Bao = Acta Pharmaceutica Sinica, 43(5), 461-6.
Wang TX, Yang XH. Reversal Effect of Isotetrandrine, an Isoquinoline Alkaloid Extracted From Caulis Mahoniae, On P-glycoprotein-mediated Doxorubicin-resistance in Human Breast Cancer (MCF-7/DOX) Cells. Yao Xue Xue Bao. 2008;43(5):461-6. PubMed PMID: 18717331.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reversal effect of isotetrandrine, an isoquinoline alkaloid extracted from Caulis Mahoniae, on P-glycoprotein-mediated doxorubicin-resistance in human breast cancer (MCF-7/DOX) cells. AU - Wang,Tian-Xiao, AU - Yang,Xiao-Hong, PY - 2008/8/23/pubmed PY - 2009/9/18/medline PY - 2008/8/23/entrez SP - 461 EP - 6 JF - Yao xue xue bao = Acta pharmaceutica Sinica JO - Yao Xue Xue Bao VL - 43 IS - 5 N2 - This study investigated the reversal effect of isotetrandrine, an isoquinoline alkaloid extracted from Caulis mahoniae, on P-glycoprotein-mediated multidrug resistance in human breast cancer doxorubicin-resistant (MCF-7/DOX) cells. RT-PCR assay and immunity histochemistry assay were used to determine the expression level of mdrl gene and P-gp in MCF-7/DOX cells to elucidate resistant character of MCF-7/DOX cells. The activity of isotetrandine to enhance doxorubicin cytotoxicity was tested using MTT (3-(4, 5-dimethyhthiazol)-2,5 -diphenyltetrazolium bromide) assay and was evaluated by the reversal fold (RF) values. Intracellular accumulation of doxorubicin was assessed by the determination of doxorubicin-associated fluorescence intensity. Effect of isotetrandrine on the expression level of P-gp in MCF-7/DOX cells was then determined by immunity histochemistry assay. The ability of isotetrandrine to inhibit P-gp function was evaluated by detecting the accumulation and efflux of rhodamine 123 (Rh123) with flow cytometry (FCM). Verapamil was employed as a comparative agent in whole experiment. The results indicated that MCF-7/DOX cells had phenotype of MDR and that the positive expression of P-gp was their resistant character. 10 microg x mL(-1) isotetrandrine could distinctly enhance cytotoxicity of DOX in MCF-7/DOX cells and reversal fold (RF) was significantly higher than that of verapamil (P < 0.05), but it hardly affected cytotoxicity of DOX in MCF-7 cells and the expression level of P-gp in MCF-7/DOX cells. The ability of isotetrandrine to inhibit P-gp function was reversible, because incubation of MCF-7/DOX cells with isotetrandrine caused a marked increase in uptake and a notable decrease in efflux of Rh123 and a marked increase of intracellular DOX concentrations. In conclusion, isotetrandrine exhibited potent effect on the reversal of P-gp-mediated MDR in vitro, suggesting that it might become a candidate of effective MDR reversing agent in cancer chemotherapy. SN - 0513-4870 UR - https://www.unboundmedicine.com/medline/citation/18717331/Reversal_effect_of_isotetrandrine_an_isoquinoline_alkaloid_extracted_from_Caulis_Mahoniae_on_P_glycoprotein_mediated_doxorubicin_resistance_in_human_breast_cancer__MCF_7/DOX__cells_ L2 - http://www.diseaseinfosearch.org/result/960 DB - PRIME DP - Unbound Medicine ER -