Objective -The discovery of the apoptosis-inducing effects of flavonoid vagonin allowed to make an assumption of existence of similar effect in others flavonoids. This study is devoted to the effects of Gratīola officinālis extract on cell culture of the human kidney cancer.Methods -Cell cultures of human kidney carcinoma -Caki-1 and SN12c were used in the study. The cells were stained with Hoechat 33258 dye. The number of living cells, cells in a state of apoptosis and mitosis were counted. The Cramer-Welch criterion (T) was used to compare the obtained data.Results -The activation of apoptosis was noted at all concentrations of the Gratiola officinalis L. extract during the first day of exposure. The apoptotic activity increased with increasing of extract concentration. After 48 hours, this activity was maintained only at a Gratiola officinalis L. extract concentration of 0.9 mg/ml. After 24 hours, the apoptotic activity of the extract was more expressed in the culture of CaKi-1. However, after 48 hours the extract induces more pronounced apoptosis in the culture of Sn12c cells. The cytotoxic activity of the extract was not differ after 24 hours in both cultures, after 48 hours it was more pronounced in the culture of CaKi-1. Conclusion -We revealed a pronounced antitumor and apoptotic activity of the Gratiola officinalis L. extract against the cultures of the kidney cancer Caki-1 and Sn12c. Apoptosis of tumor cells can be manifested in the form of pycnosis of the nucleus, the formation of apoptotic bodies and the emergence of cellular debris resulting from complete degradation of tumor cells. The apoptotic activity of the Gratiola officinalis extract depends on their concentration.

The aim of the study was to assess the effect of proline-rich polypeptide (PRP) on bone marrow stromal stem cells in vivo and in vitro and on tumour cell lines. Methods. Isolation of giant-cell tumour (GCT) stromal cells and obtaining these cell strains; obtaining normal bone marrow stromal cell strains; PRP administration to rats; bone marrow cell explantation into cultures; PRP addition to cell cultures. Results. Various routes and doses of PRP administration to rats increased the multipotent mesenchymal stromal cell (MMSC) concentration in the bone marrow. PRP addition to normal bone marrow MMSC cultures increased cell proliferation 1.5-2.5-fold, whereas PRP addition to GCT MMSC cultures inhibited cell proliferation 1.5-2-fold. Both proliferation inhibition and no PRP effect on proliferation were observed in tumour cell cultures. Conclusions. PRP administration to rats increased MMSC concentration in the normal bone marrow, and PRP addition to tissue cultures revealed opposite effects of PRP on cell proliferation.

Introduction. The molecular basis of radio- and photodynamic therapy (PDT), the mechanism of action of a number of antitumor chemotherapy drugs is oxidative stress (OS). The enzyme hemoxygenase-I (НO-1), a molecular marker of OS, is a key participant in the system of protection and adaptation of tumor cells under stress.Objective. To find out whether the sensitivity of human melanoma tumor cells to OS depends on the basal and modulator-induced levels of НO-1 expressionMaterial and methods. Human melanoma cell lines were used in the study. The expression of mRNA НO-1 in cells was studied by real-time RT-PCR, the reactive oxygen species content in cells – by flow cytometry and the cytotoxicity of drugs – by MTT assay.Results. According to our data, human melanoma cells have different basal levels of HO-1 transcription: high (3.0–3.5 o. u.) in lines MelIL, MelP, medium (1.5 o. u.) in lines MeWo, MelZ, MelIbr and low (0.5 o. e.) – MelMe, A375).There is no direct correlation between the level of basal cell expression of HO-1 and their sensitivity to the OS inducer – Н2О2. The hemin-induced increase in HO-1 expression in cells is accompanied by doubled resistance to Н2О2. It was found that HO-1 repression in the presence of apigenin was registered in melanoma cells with different basal levels, but sensitization to Н2О2 (2–4 times) was observed only for cells with medium (MeWo) and low (A375) levels of basal HO-1 expression. It was found that the decrease in basal expression of HO-1 induced by apigenin is accompanied by an increase in the reactive oxygen species content in cells.Conclusions. The results of our research allow us to recommend natural flavon apigenin, a modulator of HO-1 expression, for inclusion in the chemotherapy and PDT regimens to increase the effectiveness of human melanoma treatment.

The problem of creating antitumor drugs with new mechanisms of action that predominantly induce apoptosis is still topical. The extract of Gratiola officinalis is a potential antitumor agent containing mainly flavonoids. The aim of this research is to study the effects of Gratiola officinalis extract on activation of apoptosis and autophagy in breast adenocarcinoma SK-BR-3 and kidney carcinoma A-498 lines. Apoptotic activity of the extract was studied by flow cytofluorometry using Hoechst stain and double staining with annexin V plus propidium iodide. There was 96.3% of cells in SK-BR-3 culture in late apoptosis phase detected by flow cytofluorometry method at the extract concentration of 0.88 mg/ml, 86.3% of cells were in apoptosis by Hoechst stain. The concentration of 0.82 mg/ml caused apoptosis in half of the cells. The extract has cytoprotective activity at low concentration (0.0352 mg/ml). The cytoprotection mechanism is realized through the activation of autophagy. The maximum number of autophagosomes in kidney carcinoma cells is observed at the extract concentration of 0.056 mg/ml. Thus, Gratiola officinalis extract is able to block cytoprotective autophagy with increasing the extract concentration and to activate apoptosis in 85% of tumor cells. Detailed research should be continued to understand the mechanisms of antitumor activity of Gratiola officinalis extract.