Antiproliferative and pro-apoptotic effects of quercetin on human pancreatic carcinoma cell lines EPP85-181P and EPP85-181RDB.

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

The estimation of oxidative stress markers and apoptosis in right atrium auricles cardiomyocytes of patients undergoing surgical heart revascularisation with the use of warm blood cardioplegia.

Oxidative stress markers and apoptosis were estimated during elective surgical heart revascularization. Eight patients with good ejection fraction underwent coronary artery bypass grafting (CABG) with the use of warm blood cardioplegia. Two right atrium auricle biopsy specimens were collected before and after the operation. Specimens underwent immunocytochemical analysis of mitochondrial manganese superoxide dismutase (MnSOD) expression and apoptosis estimation by the TUNEL method. Ultrastructure analysis under electron microscope was made. Satisfactory results of the operation were obtained. After CABG the MnSOD expression increase in sections of auricles was observed through the increase of stain intensity and the percentage of cells with positive stain (from 30 to 80%). The apoptotic cells percentage remained at approximately the same level. Under the electron microscope insignificant pathological changes were observed. On this basis one may assume that in the case of cardiosurgical procedures with short aorta cross-clamping time and low operation risk level the application of cardioplegia sufficiently prevents reactive oxygen forms (ROF) cytotoxic activity although it does not inhibit the expression of oxidative stress (OS) markers. In our opinion the method of examining right atrium sections is safe and provides results comparable with other publications. It may also be a voice in the discussion on new methods of heart protection during cardiac surgery procedures

Antiproliferative and pro-apoptotic effects of quercetin on human pancreatic carcinoma cell lines EPP85-181P and EPP85-181RDB.

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

Decreased expression of p16 in ovarian cancers represents an unfavourable prognostic factor

Decreased expression of p16 may result from hypermethylation of the promoter or from deletion of the gene. It can lead to intensified proliferation of neoplastic cells and to cytostatic drug resistance. The study was aimed at the examination of prognostic value of p16 expression in relation to Ki67 and caspase-3 in ovarian cancers using immunohistochemistry. The immunohistochemical studies were performed on 73 paraffinembedded samples of ovarian cancers from 43 patients and samples from 6 healthy ovaries. We have used monoclonal antibodies against p16. ABC method and DAB were used for antigens visualisation. The intensity of the immunohistochemical reactions was appraised using the semi-quantitative IRS scale. In healthy ovaries we have shown strong reaction in the nuclei of surface epithelium. In the case of studied ovarian cancers, the reaction of a nuclear and cytoplasmic localization was obtained. The mean overall immunoreactivity score of nuclear p16 expression amounted to 5.30±3.44 SD in primary laparotomy material and 6.61±4.34 SD in secondary cytoreduction material. Statistical analysis demonstrated that lower p16 expression was typical of the younger patients and the patients who died. Kaplan- Meier’s analysis proved that lower expression of p16 was characteristic of cases with shorter overall survival. In the present study we have demonstrated that lowered p16 expression represented an unfavourable prognostic index in ovarian cancer. Lowered p16 expression was also typical for chemotherapy-resistant ceases (cases of lower caspase-3 and higher Ki67 at secondary cytoreduction expression)