“GENOME DYNAMICS AND STABILITY” – Carcinogenesis
Molecular mechanisms of carcinogenesis
Carcinogenesis is a multistep process that involves the accumulation of genetic and epigenetic changes affecting the expression of genes involved in the processes of cell growth, DNA repair, chromosome segregation, control of cell cycle and cell responses, etc. Two major classes of genes are engaged in the mechanisms of carcinogenesis: proto-oncogenes and tumor suppressor genes. Proto-oncogenes play an important role in the regulation of cell growth and proliferation, and their activation leads to cell growth stimulation. Tumor suppressor genes inhibit the regulation of cell proliferation inducing cell apoptosis, and their inactivation causes impairment of these processes. Different types of genetic and epigenetic mechanisms are involved in the activation of proto-oncogenes and inactivation of tumor suppressor genes.
Our research is focused on genetic characteristics and epigenetic status of numerous tumor suppressor genes and proto-oncogenes in breast cancer patients, in search of statistically significant correlations between abnormal gene status, clinico-pathological characteristics of patients and their survival (Bozhanov et al., 2010; Krasteva et al., 2012; Angelova et al., 2012; Antov et al., 2017).
Anticancer potential of medicinal and aromatic plants
Another research topic of the Laboratory includes evaluation of anticancer properties and elucidation of antitumor mechanisms of Bulgarian plant species used in traditional medicine.
Elaboration of medicinal products for cancer prevention and therapy based on natural substances characterized by multi-target properties, efficiency against various oncological diseases and capability to potentiate chemosensitivity without causing side effects is of great interest to modern onco-pharmacology worldwide.
The combined use of phytochemicals with conventional chemotherapeutic drugs could contribute to more beneficial therapeutic effects through additive or synergistic action between various applied chemicals, affecting one or more targets associated with the neoplastic process. The considerable diversity, valuable biological characteristics and wide distribution of medical and aromatic plants make them a promising research object in the development of novel oncotherapeutic products.
Extracts, fractions and active compounds from medicinal plant species are objects of investigation using human cancer and non-tumorigenic cell lines as a model system for evaluation of their anticancer potential. We select substances that have a strong antineoplastic effect and selectively inhibit the growth of cancer cells preserving the viability and proliferation of untransformed cells. The studied mechanisms underlying the antitumor effect of plant substances comprise inhibition of cell proliferation through cell cycle arrest at a certain phase, induction of programmed cell death (apoptosis, autophagy), anticlonogenic effects, modulation of migration, invasion, metastasis and angiogenesis processes, influence on the epigenetic processes in cancer cell – DNA methylation, histone acetylation, etc (Angelova et al., 2013; Gospodinova et al., 2014; Gospodinova et al., 2015; Gospodinova and Krasteva, 2017; Gospodinova et al., 2017). Research in this area aims to expand the knowledge on the biological activities and therapeutic potential of valuable Bulgarian plant species, thus contributing to better prevention and treatment of malignant diseases.
