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Sideritis scardica (S. scardica) is a mountain plant, endemic to the central part of the Balkan Peninsula, including the southern regions of Bulgaria. It is widely used in traditional medicine to treat some respiratory, gastrointestinal tract, or neurodegenerative diseases, but research data for its cytotoxic and anticancer properties are limited. In the present study, a hydroethanolic extract of S. scardica from region Trigrad, Bulgaria was prepared and its total polyphenolic and flavonoid content was determined. Further, its antioxidant, cytotoxic, and anticancer activities toward a mouse adenocarcinoma cell line, Colon 26 was evaluated in vitro. Higher antioxidant activity and higher total phenolic and flavonoid content were detected in the S. scardica hydroethanolic extract from region Trigrad as compared to the publish data for other ecotypes of this species. Also, the extract of S. scardica with a concentration higher than 200 µg mL-1 was found to inhibit the viability and growth of colon cancer cells but not those of the normal kidney MDCK cells pointing to a cell-specific and concentration-dependent cytotoxic effect. Thus, the current study demonstrates a high oxidation potential of S. scardica hydroethanolic extract from the region Trigrad and its cytotoxic effects on colon cancer cells when the extract was applied with concentrations of 200 µg mL-1 and higher. [ABSTRACT FROM AUTHOR]

Colon cancer is among the most common and lethal cancer types worldwide. The disease is very heterogeneous and is attributed to the accumulation of genetic and epigenetic alterations affecting specific genes involved in the regulation of cell growth, proliferation, adhesion, and survival. About 20% of patients with colon cancer are diagnosed with distant metastases which is associated with worse prognosis and survival. The search for novel natural therapeutic agents with higher effectiveness against the diseases, and milder side effects is of great interest in oncopharmacology. Medicinal plants represents valuable source of biologically active compounds with a wide range of pharmacological activities. Our previous study detected antiproliferative properties of fustin isolated from the heartwood of Cotinus coggygria Scop. against the highly metastatic colon cancer cell line Colon 26 [1]. The aim of the present work was to investigate some of the molecular mechanisms underlying the anticancer properties of fustin in colon cancer cells. For this purpose, we applied clonogenic assay to evaluate single cell capability to form a colony, fluorescence microscopy analysis after staining with Annexin V/propidium iodide to assess the proapoptotic properties of the flavonoid, wound healing assay to study antimigratory potential of fustin and quantitative reverse transcription-polymerase chain reaction analysis of the relative expression levels of genes associated with the cell cycle control, programmed cell death, and metastasis. The obtained results revealed that fustin significantly suppressed the colony-forming potential of Colon 26 cells after treatment for a period of 7 days, induced early and late apoptotic events in cancer cells and considerably inhibited cellular migratory properties, with a statistically significant decrease in cell motility compared to the untreated control observed at the 72nd hour of treatment. Transcriptional analysis of gene expression supplied information on some molecular pathways of the anticancer action of fustin and provided directions for future more detailed research. [ABSTRACT FROM AUTHOR]

Fustin is one of the main flavonoids isolated from the heartwood of Eurasian Smoke Tree (Cotinus coggygria Scop., Anacardiaceae), a medicinal plant widely applied in the Balkan folk medicine. Fustin possesses numerous biological activities, such as anti-inflammatory1, antioxidant, gastroprotective, etc.2. Regarding its anticancer properties, the flavonoid is very poorly studied. The present research aimed to assess the in vitro cytotoxic and antiproliferative potential of fustin isolated from the heartwood of Cotinus coggygria against two human skin cancer cell lines: squamous cell carcinoma (A431) and malignant melanoma (A375), and to compare these effects with the cell viability and growth inhibitory capacity on normal dermal cell line (BJ). The cytotoxic and cytostatic qualities of the flavonoid were investigated through MTT assay and microscopy observation of cell morphology after 24 h and 72 h cell treatment in a wide range of concentrations. The obtained results disclosed that fustin exhibited more pronounced antiproliferative than cytotoxic properties towards A375 and A431 skin cancer cell lines. A lack of cytotoxic and a slighter cytostatic activity against the normal BJ cell line in comparison to the cancer cells was established. It could be concluded that fustin isolated from C. coggygria possesses anti-skin cancer properties against A375 and A431 cell lines which will be further studied in details. [ABSTRACT FROM AUTHOR]

Epigenetic silencing of gene expression has become an intensively studied topic regarding breast cancer during the last years. Previous investigations have shown that hypermethylation in gene promoters is an alternative to mutations cancerrelated mechanism for inactivation of tumor suppressor gene function. The present study was designed for evaluation of promoter methylation in p53 and ATM tumor suppressor genes in Bulgarian patients with sporadic breast cancer. Sodium bisulfite conversion and methylation-specific PCR were performed on tumor DNA isolated from 55 patients with sporadic breast cancer. The data showed normal profile of methylation in the promoter region of p53 and ATM genes in all studied patients. Cases with hypermethylation were not observed. Our results did not support the involvement of p53 and ATM promoter hypermethylation in the neoplastic pathways of sporadic breast cancer. The lack of promoter hypermethylation in p53 and ATM is suggestive of a greater share of genetic aberrations in loss of tumor suppressor function of these genes and presumes the involvement of other epigenetic cancer mechanisms. To our knowledge this study provides the first data on promoter hypermethylation status of p53 and ATM genes in Bulgarian patients. [ABSTRACT FROM AUTHOR]

Medicinal plants have been intensively studied as a source of antitumor compounds. Due to the beneficial climate conditions Bulgarian herbs have high pharmacological potential. Currently, the antitumor effect of the Bulgarian medicinal plant Tribulus terrestris L. on human cancer cell lines is not studied. The main active compounds of the plant are the steroid saponins. The present study aims to analyze the effect on cell viability and apoptotic activity of total extract and saponin fraction of Bulgarian Tribulus terrestris L. on human breast cancer (MCF7) and normal (MCF10A) cell lines. Antitumor effect was established by ??? cell viability assay and assessment of apoptotic potential was done through analysis of genomic integrity (DNA fragmentation assay) and analysis of morphological cell changes (Fluorescence microscopy). The results showed that total extract of the herb has a marked dose-dependent inhibitory effect on viability of MCF7 cells (half maximal inhibitory concentration is 15 µg/ml). Cell viability of MCF10A was moderately decreased without visible dose-dependent effect. The saponin fraction has increased inhibitory effect on breast cancer cells compared to total extract. Morphological changes and DNA fragmentation were observed as markers for early and late apoptosis predominantly in tumor cells after treatment. Apoptotic processes were intensified with the increase of treatment duration. The obtained results are the first showing selective antitumor activity of Bulgarian Tribulus terrestris L. on human cancer cells in vitro. Apoptotic processes are involved in the antitumor mechanisms induced by the herb. This results give directions for future investigations concerning detailed assessment of its pharmacological potential. [ABSTRACT FROM AUTHOR]

Purpose: To elucidate the anticancer mechanism and molecular targets of the aqueous fraction from Cotinus coggygria leaf extract in A375 malignant melanoma cells. Methods: Aqueous ethanol extract from the leaves of C. coggygria was fractionated into the aqueous and chloroform fractions by solvent-solvent partition. A375 cells were treated with the aqueous fraction at various concentrations and incubated for 72 h. The effect of the aqueous fraction on programmed cell death by staining with Annexin V/Propidium iodide ias well as on cell viability and adhesion through labeling with fluorescein diacetate were determined under fluorescence microscopy. In addition, the clonogenicity assessment, comet assay evaluation of genotoxic properties, characterization of thermodynamic behavior of cells by differential scanning calorimetry, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) on the expression of genes involved in processes of apoptosis and cell cycle control were determined. Results: The number of viable adherent cells was reduced by 38.00 and 85.06 % at 20 and 80 µg/mL, respectively compared to untreated cells. In addition, a significant, dose-dependent reduction in the clonogenicity of melanoma cells was observed, culminating in an almost complete inhibition of cancer cells colony-forming ability at 40 and 60 µg/mL of the fraction. Treatment with the fraction increased comets of Classes 3 and 4 to 35 %, while comets of Class 5, which corresponds to the highest level of DNA fragmentation, increased to 2.25 %. Also, the gene damage index (GDI) was highest (1.2) at the concentration of 40 µg/mL. Furthermore, the expression levels of BAX, CASP8 and CDKN1A were upregulated and MYC expression decreased after treatment with the aqueous fraction. Conclusion: Cotinus coggygria possesses significant in vitro anti-melanoma potential. Future studies will be focused on the in vivo assessment of its therapeutic qualities in experimental animals. [ABSTRACT FROM AUTHOR]

The aim of the present work was to investigate some of the molecular mechanisms and targets of the anticancer action of the bioflavonoid fustin isolated from the heartwood of Cotinus coggygria Scop. in the triple-negative breast cancer cell line MDA-MB-231. For this purpose, we applied fluorescence microscopy analysis to evaluate apoptosis, necrosis, and mitochondrial integrity, wound healing assay to study fustin antimigratory potential and quantitative reverse transcription-polymerase chain reaction to analyze the expression of genes associated with cell cycle control, programmed cell death, metastasis, and epigenetic alterations. A complex network-based bioinformatic analysis was also employed for protein-protein network construction, hub genes identification, and functional enrichment. The results revealed a significant induction of early and late apoptotic and necrotic events, a slight alteration of the mitochondria-related fluorescence, and marked antimotility effect after fustin treatment. Of 34 analyzed genes, seven fustin targets were identified, of which CDKN1A , ATM , and MYC were significantly enriched in pathways such as cell cycle, intrinsic apoptotic signaling pathway in response to DNA damage and generic transcription pathway. Our findings outline some molecular mechanisms of the anticancer action of fustin pointing it out as a potential oncotherapeutic agent and provide directions for future in vivo research., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)