[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: Polyphenols are present in several edible plants and for many years induce high interest mainly due to their antioxidative and anti-inflammatory influence. At present, numerous studies are conducted on antineoplastic effects of the compounds. One of most effective biopolyphenols involves the flavonol quercetin. Our studies aimed at evaluation of antiproliferative and pro-apoptotic effects of quercetin alone and in combinations with daunorubicin on cells of human pancreatic carcinoma lines. The experiments were conducted on two cell lines, sensitive to daunorubicin EPP85-181P line, and its resistant variant EPP85-181RDB. Effect of studied substances on cell proliferation was detected using sulphorhodamine B (SRB) protein staining method. Apoptotic damage was estimated using comet and TUNEL techniques. Our data demonstrated that quercetin exerted cytotoxic action on cells of the both neoplastic cell lines in concentration-dependent manner. In the case of EPP85-181RDB cell line, quercetin seemed to sensitize resistant cells to daunorubicin. In parallel, the effect of both substances on the sensitive cell line was synergistic. Results of the studies confirmed that quercetin may probably break resistance of neoplastic cells to chemotherapy. On the other side, studied flavonol augmented action of cytostatic drug in case of sensitive tumour cells what suggest, that it might allow to decrease dosage of cytostatic drugs and reduce negative side effects of the treatment.
Folia Histochemica et Cytobiologica 01/2010; 48(2):222-9. · 1.10 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to evaluate the influence of pressure applied while assessing the graft's tightness on the expression of adhesion molecules. Another goal was to find a correlation between the type of fluid (heparynized blood or saline) used during preparation of the conduit and the expression of the adhesion molecules. Saphenous vein fragments were obtained from 48 patients who had undergone coronary artery surgery. Expression of the following particles was evaluated: CD 31, ICAM 1, VCAM 1 and P-selectin. Expression of the CD 31 molecule was described as a percentage of the inner surface of the vessel showing positive immunocytochemical reaction. Expression of the remaining molecules (ICAM 1, VCAM 1, P-selectin) was assessed as the percentage of the surface, determined by CD 31 positive reaction. The expression of the adhesion molecules (ICAM 1, VCAM 1, P-selectin) was higher in the fragments of the vein exposed to pressure. In reference to VCAM 1 the difference, as compared with the control group, was: 250% in the fragments infused with blood and 270% in the fragments infused with saline, respectively. The differences for the ICAM 1 were approximately 300% in both experimental groups and 450% for the P-selectin with subtle differences between the two experimental groups. The loss of the endothelial surface (determined by the expression of the CD 31 antigen) was similar in the specimens flushed either with blood or saline, which indicates that the major cause of damage of the endothelium is influence of pressure on the conduit's wall. Mechanical widening of vessels results in the increased expression of the adhesion molecules on the surface of the endothelial cells, and, as a consequence, leads to rise in the leukocyte adhesion and loss of the functional properties of the transplanted veins.
In vivo (Athens, Greece) 01/2007; 21(5):785-9. · 1.15 Impact Factor