Oncolytic activity of a new group of non-classified rotavirus of Reoviridae family on human epidermoid carcinoma A431 growth.

e15272 Background: Significant increase of malignant tumors` incidence all over the world in spite of vast arsenal of anticancer drugs and their combinations challenges the oncologists to develop new approaches to tumor treatment. Application of oncolytic virus is considered to be rather promising. Here we studied two strains of the new group of non-classified rotavirus of Reoviridae family (RVK): 100 and 228 ( http://jbks.ru/archive/issue-10/article-6 ). RVK are attenuated non-pathogenic virus growing on pig embryo kidney cell culture with concentration 5·109 per 1 ml. The aim of the study was to assess the effect of two RVK strains (100 and 228) on the growth of human epidermoid carcinoma A431 transplanted to nude mice in vivo. Methods: Mice Balb/cNude 22-24 g body weight (n = 13) were injected with 4х106 cells of human epidermoid carcinoma A431 subcutaneously in SPF-area of vivarium. After formation of palpable tumors (1 week after transplantation) administration of alive RVK strains 100 and 228 was performed. The 3rd group was the control one and received 0.85% NaCl. The injections were performed once a week 0.3 ml. Tumor growth rate and its` volume were measured. 1 week after the completion of the course mice were sacrificed, tumors were weighted and their morphology was studied. Results: In mice injected with RVK tumor growth inhibition developed in early date after the injection and was statistically significant within 30 - 40 days of monitoring only after the administration of strain 100. In these animals tumor weight was 2.6 times lower than in control mice (6.3±3.0 и 16.6±2.3 g respectively, р < 0.05), in mice having received strain 228 it was 1.7 times less tan in controls. Layers of high-grade sqamous carcinoma cells without keratinization with inflammatory and necrotic foci were observed in tumors of control mice while in tumors inhibited by RVK dystrophic changes and fragmentation, inflammation in places severe and necrotic foci were seen. Implication of the strain 100 resulted in 2-3 time reduction of tumor size, decrease of tumor cells` layers, mononuclear infiltration. Conclusions: In the in vivo model of human epidermoid carcinoma A431 transplanted to nude mice the inhibition of tumor growth under RVK administration was established. Our results confirm the oncolytic activity in RVK, particularly in strain 100.

Recombinant analogue of the human protein SLURP-1 inhibits the growth of multicellular carcinoma cell spheroids

The present study showed that the recombinant analogue of SLURP‑1 effectively inhibits the growth of a 3D model of tumors - multicellular spheroids from human epidermoid carcinoma A431 cells and human lung adenocarcinoma A549 cells. The combined application of SLURP‑1 with gefitinib (inhibitor of epidermal growth factor receptor (EGFR)) leads to the synergistic antiproliferative effect on spheroids from A431 cells. The results obtained suggest the possibility for design of first-in-class anticancer drugs based on recombinant SLURP‑1.

Multifloroside Suppressing Proliferation and Colony Formation, Inducing S Cell Cycle Arrest, ROS Production, and Increasing MMP in Human Epidermoid Carcinoma Cell Lines A431

Multifloroside (4), together with 10-hydroxyoleoside 11-methyl ester (1), 10-hydroxyoleoside dimethyl ester (2), and 10-hydroxyligustroside (3), are all secoiridoids, which are naturally occurring compounds that possess a wide range of biological and pharmacological activities. However, the anti-cancer activity of 1–4 has not been evaluated yet. The objective of this work was to study the anti-cancer activities of 1–4 in the human epidermoid carcinoma cell lines A431 and the human non-small cell lung cancer (NSCLC) cell lines A549. The results indicate that 1–4 differ in potency in their ability to inhibit the proliferation of human A431 and A549 cells, and multifloroside (4) display the highest inhibitory activity against A431 cells. The structure-activity relationships suggest that the o-hydroxy-p-hydroxy-phenylethyl group may contribute to the anti-cancer activity against A431 cells. Multifloroside treatment can also inhibit cell colony formation, arrest the cell cycle in the S-phase, increase the levels of reactive-oxygen-species (ROS), and mitochondrial membrane potential (MMP), but it did not significantly induce cell apoptosis at low concentrations. The findings indicated that multifloroside (4) has the tendency to show selective anti-cancer effects in A431 cells, along with suppressing the colony formation, inducing S cell cycle arrest, ROS production, and increasing MMP.

The efficacy of lyticase and β-glucosidase enzymes on biofilm degradation of Pseudomonas aeruginosa strains with different gene profiles

Background Pseudomonas aeruginosa is a nosocomial pathogen that causes severe infections in immunocompromised patients. Biofilm plays a significant role in the resistance of this bacterium and complicates the treatment of its infections. In this study, the effect of lyticase and β-glucosidase enzymes on the degradation of biofilms of P. aeruginosa strains isolated from cystic fibrosis and burn wound infections were assessed. Moreover, the decrease of ceftazidime minimum biofilm eliminating concentrations (MBEC) after enzymatic treatment was evaluated. Results This study demonstrated the effectiveness of both enzymes in degrading the biofilms of P. aeruginosa. In contrast to the lyticase enzyme, β-glucosidase reduced the ceftazidime MBECs significantly (P < 0.05). Both enzymes had no cytotoxic effect on the A-549 human lung carcinoma epithelial cell lines and A-431 human epidermoid carcinoma cell lines. Conclusion Considering the characteristics of the β-glucosidase enzyme, which includes the notable degradation of P. aeruginosa biofilms and a significant decrease in the ceftazidime MBECs and non-toxicity for eukaryotic cells, this enzyme can be a promising therapeutic candidate for degradation of biofilms in burn wound patients, but further studies are needed.