Study of tea polyphenol as a reversal agent for carcinoma cell lines' multidrug resistance (study of TP as a MDR reversal agent).
The aim of this study was to examine MDR1 expression product P-glycoprotein (Pgp) and study the effect and mechanism of tea polyphenol (TP) in reversion of multidrug resistance (MDR) in carcinoma cell lines. Immunocytochemical method was used for qualitative detection of Pgp. A comparative study of cytotoxicity and multidrug resistance reversion effect was made by MTT assay for tea polyphenol and quinidine in MCF-7 and MCF-7/Adr cell lines. The multidrug resistance reversion effect and mechanism were studied by measuring the uptake of 99mTc-tetrofosmin in the carcinoma cell lines. (1) The Pgp overexpression in MCF-7/Adr cells was found to be strong positive, while the Pgp expression of MCF-7 was negative. (2) Although both tea polyphenol and quinidine could not remarkably change the toxicity of adriamycin to MCF-7, they could improve the sensitivity of MCF-7/Adr to adriamycin. The reversion index of tea polyphenol and quinidine was 3 and 10 respectively. (3) The cellular uptake of 99mTc-tetrofosmin was remarkably lower in MCF-7/Adr than in MCF-7. The uptake of 99mTc-tetrofosmin in MCF-7/Adr exhibited a 4, 13, 16 fold increase in the presence of 200, 400 and 500 microg/ml of tea polyphenol respectively. The uptake of 99mTc-tetrofosmin in MCF-7/Adr exhibited only a 4-fold increase in the presence of 200 microM of quinidine. Immunocytochemistry can detect P-glycoprotein expression level qualitatively. Tea polyphenol is not only an anti-tumor agent, but also a multidrug resistant modulator similar to quinidine. The multidrug resistance reversion mechanism of tea polyphenol seems to be its inhibition of the activity of P-glycoprotein. Tea polyphenol has the advantage of very low toxicity in tumor treatment.
Zhu
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Department of Technical Physics, Peking University, 100871, People's Republic of, Beijing, China. zhuaizhi@263.net
Wang
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Guo
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D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D004347:Drug Interactions; D018432:Drug Resistance, Multiple; D005419:Flavonoids; D009943:Organophosphorus Compounds / Q000493:pharmacokinetics / Q000494:pharmacology*; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics / Q000494:pharmacology*; D010636:Phenols / Q000302:isolation & purification / Q000633:toxicity*; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D011108:Polymers / Q000302:isolation & purification / Q000633:toxicity*; D059808:Polyphenols; D011802:Quinidine / Q000494:pharmacology / Q000627:therapeutic use; D013662:Tea; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005419:Flavonoids; D009943:Organophosphorus Compounds; D015609:Organotechnetium Compounds; D010636:Phenols; D010936:Plant Extracts; D011108:Polymers; D059808:Polyphenols; D013662:Tea; C078700:technetium tc-99m tetrofosmin; D011802:Quinidine