Macrophage-derived chemokine CCL22 and regulatory T cells in ovarian cancer patients.

The study was undertaken to evaluate macrophage-derived chemokine (CCL22) levels in the peritoneal fluid (PF) and plasma of patients with ovarian cancer (n = 93) in relation to regulatory T cells (Tregs; n = 75). The peritoneal fluid CCL22 concentrations were significantly higher in epithelial ovarian cancer (EOC) patients than in patients with benign tumors-serous cystadenoma (n = 32). There was no difference in plasma levels of CCL22 in EOC patients compared with the non-cancer and healthy volunteers (n = 10). There were no significant differences in the plasma and PF CCL22 levels based on tumor grade. However, women with stage IV FIGO (International Federation of Gynecologists and Obstetricians) had significantly higher plasma CCL22 levels than patients with stages I and III. Women with stage I FIGO had significantly higher PF CCL22 levels than patients with stages II and III. Women with endometrioid cystadenocarcinoma had higher PF CCL22 levels than women with undifferentiated carcinoma. The percentage of tumor-infiltrating Tregs (11.06 %) was significantly higher compared to PF (3.05 %) and peripheral blood (PB) (2.01 %). Moreover, the percentage of Tregs was higher in the PF than in the PB of EOC patients. There were no significant differences in the PB, PF, and tumor-infiltrating Tregs percentage based on tumor stage, grade, or histology. Elevated levels of CCL22 found in the ascites could create a chemokine gradient aiding in Treg cells migration. Increased Tregs percentage in the local microenvironment of ovarian cancer might be an important mechanism of immunosuppression.

The effect of quercetin on pro-apoptotic activity of cisplatin in HeLa cells.

It is well known that some tumour cells are very resistant to chemotherapy-induced cell death which indicate poor prognosis for patients. Thus the aim of the present study was to investigate the effect of quercetin on pro-apoptotic activity of cisplatin in human cervix carcinoma cells (HeLa). Three variants of experiments were performed. In the first one cells were incubated with studied drugs separately for 8 and 24h. In the second, drugs were added to the culture medium simultaneously. In third cisplatin or quercetin addition was followed by subsequent quercetin or cisplatin treatment, respectively. We observed different apoptotic effects, dependent on the drug succession. Preincubation of cells with quercetin followed by cisplatin treatment appeared to be the most effective and was correlated with strong activation of caspase-3 and inhibition of both heat shock proteins (Hsp72) and multi-drug resistance proteins (MRP) levels. Our results indicate that quercetin pretreatment sensitizes HeLa cells to cisplatin-induced apoptosis in HeLa cells.

The effect of quercetin on the expression of heat shock proteins and apoptosis induction in monkey kidney cell line GMK.

The present study was designed to investigate whether quercetin, a very common flavonoid widely distributed in many plants, can induce apoptosis in monkey kidney cells (GMK). Involvement of the expression of heat shock proteins Hsp72, Hsp73, Hsp27 and the significance of cell culture model in this process were also examined. The studies have shown that quercetin alone and in combination with the heat shock can induce apoptosis and necrosis in vitro in the studiedcells, but the percentage of affected cells did not exceed 3.9%. In the same experimental conditions, the expression of Hsp 73, Hsp72 and Hsp27 increased in cells cultured in two-dimensional system and decreased in three-dimensional model. This indicates that strong inhibition of heat shock proteins in GMK cells is not correlated with an adequate increase in the sensitivity of cells to undergo apoptosis. It also shows that the sensitivity on the manifested by Hsp expression and apoptosis induction, depends on the culture model and culture conditions.

The effect of quercetin on apoptosis and necrosis induction in human colon adenocarcinoma cell line LS180.

Quercetin is a very common flavonoid widely distributed in many plants. The flavonoid intake has been linked to the prevention of some human diseases including cancer. Quercetin inhibits heat shock protein expression and in this way triggers apoptosis of tumor cells. The present study was designed to investigate whether quercetin exerts cytotoxic activity against human colon adenocarcinoma cells. The studies have shown that quercetin alone and in combination with the heat shock can induce apoptosis and necrosis in vitro in human colon adenocarcinoma cells (LS 180). Relationships between heat shock proteins and quercetin in this phenomenon are discussed.