Quercetin as a Potential Modulator of P-Glycoprotein Expression and Function in Cells of Human Pancreatic Carcinoma Line Resistant to Daunorubicin

被引:66
作者
Borska, Sylwia [1 ]
Sopel, Miroslaw [1 ]
Chmielewska, Magdalena [1 ]
Zabel, Maciej [1 ,2 ]
Dziegiel, Piotr [1 ,2 ,3 ]
机构
[1] Med Univ, Dept Histol & Embryol, PL-50368 Wroclaw, Poland
[2] Poznan Univ Med Sci, Dept Histol & Embryol, PL-60781 Poznan, Poland
[3] Lower Silesian Ctr Oncol, PL-53413 Wroclaw, Poland
关键词
quercetin; daunorubicin; P-glycoprotein; multidrug resistance; MULTIDRUG-RESISTANCE; DIETARY FLAVONOIDS; CANCER PREVENTION; MECHANISMS; INHIBITORS; TRANSPORT; BIOAVAILABILITY; ANTIOXIDANT; CHEMISTRY; APOPTOSIS;
D O I
10.3390/molecules15020857
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
P-glycoprotein (P-gp) is one of the ABC transporters responsible for the resistance of several tumours to successful chemotherapy. Numerous agents are capable of interfering with the P-gp-mediated export of drugs but unfortunately most of them produce serious side effects. Some plant polyphenols, including the flavonol quercetin (Q), manifest anti-neoplastic activity mainly due to their influence on cell cycle control and apoptosis. Reports are also available which show that Q may intensify action of cytostatic drugs and suppress the multidrug resistance (MDR) phenomenon. The study aimed at determination if Q sensitizes cells resistant to daunorubicin (DB) through its effect on P-gp expression and action. The experiments were conducted on two cell lines of human pancreatic carcinoma, resistant to DB EPP85-181RDB and sensitive EPP85-181P as a comparison. Cells of both lines were exposed to selected concentrations of Q and DB, and then membranous expression of P-gp and its transport function were examined. The influence on expression of gene for P-gp (ABCB1) was also investigated. Results of the studies confirmed that Q affects expression and function of P-gp in a concentration-dependent manner. Moreover it decreased expression of ABCB1. Thus, Q may be considered as a potential modulator of P-gp.
引用
收藏
页码:857 / 870
页数:14
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