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Current plant-derived anticancer therapeutics aim to reach higher effectiveness, to potentiate chemosensitivity and minimize the toxic side effects compared to conventional chemotherapy. Cotinus coggygria Scop. is a herb with high pharmacological potential, widely applied in traditional phytotherapy. Our previous study revealed that leaf aqueous ethanolic extract from C. coggygria exerts in vitro anticancer activity on human breast, ovarian and cervical cancer cell lines. The objective of the present research was to investigate possible molecular mechanisms and targets of the antitumor activity of the extract in breast cancer MCF7 cells through analysis of cell cycle and apoptosis, clonogenic ability assessment, evaluation of the extract genotoxic capacity, characterization of cells thermodynamic properties, and analysis on the expression of genes involved in cellular epigenetic processes. The obtained results indicated that in MCF7 cells C. coggygria extract causes S phase cell cycle arrest and triggers apoptosis, reduces colony formation, induces DNA damage, affects cellular thermodynamic parameters, and tends to inhibit the relative expression of DNMT1, DNMT3a, MBD3, and p300. Further studies on the targeted molecules and the extract anti-breast cancer potential on animal experimental model system, need to be performed in the future.

Introduction: Due to the high prevalence of viral infections having no specific treatment and the constant emergence of resistant viral strains, searching for effective antiviral compounds is crucial. The present study explores in vitro the antiviral activity of ethanolic extract from aerial parts of Tanacetum vulgare L. against viral strains of three taxonomic groups, including agents that cause socially significant diseases in humans for which antiviral chemotherapy is indicated, namely coxsackievirus B1 (family Picornaviridae), herpes simplex virus type 1 (family Herpesviridae) and influenza A virus (family Orthomyxoviridae). Aim: The aim of the current study was to evaluate antiviral activity of ethanolic extract from herbaceous plant Tanacetum vulgare L. against some important human viruses for which antiviral chemotherapy is needed and to characterize extract for its antioxidant activity in vitro. Materials and methods: The crude aqueous ethanolic extract from aerial parts of Tanacetum vulgare L. contained flavonoids determined as apigenin, coumarins determined as aesculin, tannic compounds determined as tannin, and others. Antiviral activity of ethanolic extract from herbaceous plant Tanacetum vulgare L. against coxsackievirus B1, influenza A and herpes simplex virus type 1 was evaluated by viral yield reduction technique. The total antioxidant activity was determined by measuring the capacity of the sample to inhibit the generation of thiobarbituric acid reactive substances (TBARS). Results: The results show that the extract has the lowest toxicity on the MDBK cell line and similar cytotoxicity in Hep-2, whereas in the MDCK cells it has more than twice the highest toxicity. Testing the antiviral activity of Tanacetum vulgare L. extract revealed a slight inhibition of replication of HSV-1 with a selective index of 7.07 and IAV/H3N2 (SI = 3.69) but no specific antiviral effect against CVB1 replication was found. The evaluation of the antioxidant activity showed great antioxidant activity of the ethanolic extract from T. vulgare – 26 mmol/l for the applied 20 mg/ml extract. Conclusion: The crude extract from aerial parts of the medicinal plant Tanacetum vulgare L. demonstrated low cytotoxicity in Hep-2, MDBK and moderate cytotoxic effects in MDCK cells. It exerted significant antiviral activity against HSV-1 as determined by the recorded inhibition of viral replication, the blockage of virus entry - absorption stage and direct virucidal effects on extracellular virions. The observed effect when testing Tanacetum’s extract on influenza A H3N2 virus infection in vitro was milder, which probably resulted from the interference with the cellular pathways involved in the replication cycle. The presence of virucidal and adsorption-suppressing activity but the absence of viral replication inhibitory effects against CBV-1 suggests a possible interaction of the extract’s components with viral capsid proteins or related cell receptors.

Cotinus coggygria Scop. leaf aqueous ethanolic extract was examined for its in vitro antiproliferative and antioxidant activity. Antiproliferative effect was assessed on four human gynecological cancer cell lines: breast (MCF7, T47D), cervical (HeLa) and ovarian (A2780) and compared to the cell growth inhibitory effect on non-cancerous breast epithelial cell line MCF10A using MTT cell proliferation assay. Radical scavenging assay with DPPH was applied to evaluate antioxidant potential of the extract. The obtained results showed that the herb inhibited cell growth of all of the tested cancer cell lines and the highest was the cytostatic effect on A2780 cells with a half maximal inhibitory concentration (IC50) value of 30.8 μg/ml. For the other cell lines the IC50 values were in the range of 55-122.7 μg/ml. Additionally, the extract exerted considerably weaker reduction in cell proliferation of the non-cancerous cell line MCF10A compared to cancer cells, which indicates for antiproliferative selectivity. C. coggygria extract showed high free radical scavenging activity with an IC50 value of 11.2 μg/ml. The obtained data provide evidence for pharmacological potential of the tested extract and future more detailed studies concerning the molecular mechanisms of the anticancer effect of the herb are needed.

Due to the high prevalence of viral infections having no specific treatment and the constant emergence of resistant viral strains, searching for effective antiviral compounds is crucial. The present study explores in vitro the antiviral activity of ethanolic extract from aerial parts of.The aim of the current study was to evaluate antiviral activity of ethanolic extract from herbaceous plant.The crude aqueous ethanolic extract from aerial parts of.The results show that the extract has the lowest toxicity on the MDBK cell line and similar cytotoxicity in Hep-2, whereas in the MDCK cells it has more than twice the highest toxicity. Testing the antiviral activity of.The crude extract from aerial parts of the medicinal plant.

Recently, graphene oxide (GO) has been increasingly investigated for its biomedical and biological applications, including cancer research. The interest is set on GO chemical modifications and their implications in the development of therapeutic approaches for various diseases. Recent data have demonstrated that PEGylation of nanoparticles (NPs) improves NPs solubility and stability in physiological solutions and alters their reactivity toward cancer cells. In this work, we have evaluated the effect of PEGylated GO nanosheets on the migratory and proliferation ability of A375 melanoma cells, used as a cancer cell model and have compared it to normal kidney MDCK cells. Both types of GOs, pristine and PEGylated, demonstrated an inhibitory effect on the cancer cells proliferation and mobility while on normal MDCK cells the effect of GO was significantly weaker at 48 hours of exposure suggesting that cancer A375 cells were more sensitive to GO and GO-PEG treatment. In general, PEGylation mitigates the inhibitory effect of GO on the growth and migratory ability of melanoma cells. Our results prove that the effects of both GOs NPs on cancer cells proliferation and mobility are dose-, NPs- and cell-type-dependent, hence providing a rationale for future design and use of graphene-based nanomaterials for cancer research.

Promoter hypermethylation was shown to be involved in human cancerogenesis through silencing gene expression. Several studies were dedicated to explore the frequency and clinical significance of BRCA1 hypermethylation in sporadic breast cancer to identify a specific molecular and clinico-pathological phenotype. However the available data are limited and rather too heterogeneous. In this study we investigated the level of methylation in the promoter region of BRCA1 and its correlation with clinico-pathological and molecular characteristics in a group of 135 Bulgarian patients. Methylation specific PCR was applied to determine methylation status of tumor samples. Clinical impact of BRCA1 hypermethylation was estimated using standard statistical methods including Fisher's exact and the Chi-squared tests, the Kaplan-Meier method, the univariate and multivariate Cox proportional hazards regression model. We found that hypermethylation was present in 17.04% of the cases (23/135). Patients with hypermethylation in BRCA1 displayed favorable clinical status as their tumors were smaller in size (P = 0.066), lacked p53 gene mutations (P = 0.073) and were of lobular type (P = 0.046). The presence of hypermethylation was weakly associated with better overall survival (P = 0.2) with a hazard ratio of 0.47 (95% CI 0.14-1.54, P= 0.213). Our study provides the first data on the BRCA1 hypermethylation of Bulgarian patients and contributes to elucidation of its clinical significance in sporadic breast cancer.

Checkpoint kinase 2 (CHEK2) is a DNA damage-activated protein kinase implicated in cell cycle checkpoint control. The significance of CHEK2 alterations for breast cancer incidence and clinical behavior is not clear. In this study we determined the mutational spectrum and the level of promoter hypermethylation of CHEK2 gene in a group of 145 Bulgarian patients with breast cancer. A special emphasis was put on the clinical impact of CHEK2 alterations for breast cancerogenesis. PCR-SSCP-sequencing analysis of the entire coding sequence of CHEK2 gene was performed to estimate the mutational profile of tumor samples. Methylation-sensitive SSCP was applied to determine the methylation status in CpG clusters implicated in CHEK2 silencing. Clinical significance of CHEK2 alterations was evaluated using standard statistical methods. Mutations in CHEK2 were identified in 9.65 % of the patients. Two novel missense substitutions Thr476Met (C >T) and Ala507Gly (C>G), and a novel silent variant Glu79Glu (A>G) were registered. However, hypermethylation was not found in any of the studied cases. Comparison with clinical characteristics showed that CHEK2 positive women have predominantly lobular type of breast carcinoma (р=0.04) and PR+ status (p=0.092). CHEK2 mutations correlated significantly with ATM+ status (p=0.046). All patients with the Glu79Glu variant were progesterone receptor positive (p=0.004). A decrease in overall survival (p = 0.6301) and a threefold increased independent risk of death (HR = 3.295, 95%CI 0.850-12.778, p = 0.085) in CHEK2+patients was found. Our data indicate the significance of CHEK2 gene alterations in contrast to promoter hypermethylation in breast cancerogenesis. Specificity of CHEK2 mutational profile for the Bulgarian population was found. Though CHEK2 mutational status correlated with more favorable clinical characteristics, including positive progesterone receptor and lobular histological type, it independently increased the risk of death in these patients.