ABSTRACT
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.
Subject(s)
Anacardiaceae/chemistry , Breast Neoplasms/drug therapy , Cell Proliferation/drug effects , Plant Extracts/pharmacology , Apoptosis/drug effects , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Cell Cycle Checkpoints/drug effects , DNA (Cytosine-5-)-Methyltransferase 1/genetics , DNA (Cytosine-5-)-Methyltransferases/genetics , DNA Damage/drug effects , DNA Methyltransferase 3A , DNA-Binding Proteins/genetics , Epigenesis, Genetic/drug effects , Female , Gene Expression Regulation, Neoplastic/drug effects , Humans , MCF-7 Cells , Plant Extracts/chemistry , Plant Leaves/chemistryABSTRACT
Barley nucleolus organizing regions (NORs) were previously found to behave as prominent aberration hot-spots after treatment with some restriction endonucleases. The ability of MspI for directed induction of double-strand breaks in barley ribosomal DNA was further analyzed. Ionizing radiation-produced strand breakage within the ribosomal gene clusters was also a subject of investigation. Reconstructed barley karyotypes T1586 and T35 with normal and increased expression of rRNA genes were utilized to evaluate the relationship between transcriptional activity and damage induction. Scanning densitometry of the hybridization profiles revealed that MspI is generating double-strand breaks in barley rDNA with efficiency being independent from the NOR activity. Damage induction observed after treatment with gamma-rays was also not influenced by the transcriptional status of the ribosomal genes. A tendency towards restoration of rDNA integrity after irradiation of both germinating and dry seeds was observed which is indicative for the efficient recovery of double-strand breaks in barley ribosomal DNA.
