EFFECTS OF DEXTRAN-GRAFT-POLYACRYLAMIDE/ZnO NANOPARTICLES ON PROSTATE CANCER CELL LINES IN VITRO.

BACKGROUND: The combination of zinc oxide (ZnO) nanoparticles (NPs) with carriers enhances the anticancer effect of nanocomposites. AIM: To explore the mechanisms of cytotoxic action of dextran-graft-polyacrylamide (D-g-PAA/ZnO) NPs against prostate cancers cell lines in vitro. MATERIALS AND METHODS: Dextran-polyacrylamide was used as a matrix for the synthesis of ZnO NPs. Prostate cancer cells LNCaP, DU-145 and PC-3 were treated with D-g-PAA/ZnO NPs. The expression of Bax, Bcl-2, p53 and Ki-67 was studied using immunocytochemical analysis. Cytomorphological changes in cells were detected after their incubation with nanocomposites for 24 h. RESULTS: The treatment with D-g-PAA/ZnO NPs caused the increase in the Bax and p53 and the decrease in Ki-67 and Bcl-2 expression. Morphological changes associated with apoptosis were registered: decrease in cell size, appearance of cytoplasmic vacuolation, condensation of chromatin, blebbing. CONCLUSIONS: Treatment with D-g-PAA/ZnO nanocomposite led to the initiation of apoptotic cell death in prostate cancer cells in vitro.

EXPRESSION OF OSTEOPONTIN AND OSTEONECTIN IN BREAST AND PROSTATE CANCER CELLS WITH DIFFERENT SENSITIVITY TO DOXORUBICIN.

BACKGROUND: According to modern literature, osteopontin (OPN) and osteonectin (ON) are involved not only in the formation of the aggressive phenotype of malignantly transformed cells, but also in the realization of cytotoxic effects of some antitumor drugs. AIM: To study the changes of the expression of OPN and ON and their mRNAs (SPP1 and SPARC) upon exposure to doxorubicin (Dox) in breast cancer (BCa) and prostate cancer (PCa) cell lines with different sensitivity to Dox. MATERIALS AND METHODS: Cell lines of BCa (MCF-7 and MDA-MB-231) and PCa (LNCaP and DU-145) were cultured in the presence of Dox at IC30 concentrations for 24 h. OPN and ON levels were assessed by immunocytochemical (ICH) and Western blot analysis. SPP1 and SPARC mRNA levels were assessed by quantitative PCR. RESULTS: Dox treatment resulted in the significant decrease in the expression of both OPN and ON in MCF-7 and LNCaP cells. Similarly, Dox treatment downregulated both SPP1 and SPARC in MDA-MB-231 and DU-145 cells. Dox did not affect ON expression in MDA-MB-231 and DU-145 cells although the significant decrease in the level of SPARC mRNA has been evident. In contrast, no significant differences in SPP1 and SPARC mRNA levels were detected in LNCaP cells. CONCLUSION: The changes in the expression of OPN and ON proteins and their corresponding genes in BCa and PCa cells may be related to the intrinsic mechanisms of Dox effects in cells differing by malignant phenotype and Dox sensitivity.

Effect of 3-substituted 1,4-benzodiazepin-2-ones on bradykinin-induced smooth muscle contraction.

Biochemical properties of 3-substituted 1,4-benzodiazepine determined by the characteristics of their chemical structure. Influence of 3-substituted 1,4-benzodiazepin-2-ones on maximal normalized rate and amplitudes of isometric smooth muscle contraction in rats was investigated. Compounds MX-1775 and MX-1828 demonstrated the similar inhibition effect on bradykinin-induced contraction of smooth muscle like competitive inhibitor des-arg9-bradykinin-acetate to bradykinin B2-receptors. MX-1626 demonstrated unidirectional changes of maximal normalized rate and force of smooth muscle that proportionally depended on bradykinin concentration in the range 10-10-10-6 M. MX-1828 has statistically significant decrease of normalized rate of smooth muscle contraction for bradykinin concentrations 10-10 and 10-9 M by 20.7 and 8.6%, respectively, but for agonist concentration 10-6 M, this parameter increased by 10.7% and amplitude was reduced by 29.5%. Compounds MX-2011, MX-1785 and MX-2004 showed no natural effect on bradykinin-induced smooth muscle contraction. Compounds MX-1775, MX-1828, MX-1626 were selected for further research of their influence on kinin-kallikrein system and pain perception.