RESUMO
BACKGROUND: Regulatory degradation of intracellular proteins plays an essential role in most biological processes, particularly in the control of cell proliferation and differentiation. In eukaryotes, intracellular proteolysis is largely provided by the Ubiquitin / Proteasome system. Alterations and dysfunction of protein degradation by the Ubiquitin / Proteasome system, such as transcription factors, cell cycle regulators or tumor suppressor proteins, have been linked to human. Pathologies, including blood cancers. Mainly localized in the nucleus and cytoplasm of cells, the proteasome can be detected in the cell culture supernatant or in the peripheral blood of patients. This study deals with the problems of the search for serum markers specific to certain pathologies and which would be useful in the prevention, diagnosis and monitoring of cancers and which could be used as a therapeutic tool. METHODS: The functional and quantitative analysis of the proteasome is carried out at the serum and subcellular level during a pathological phenomenon in a population of 145 Moroccan patients (sex ratio: 1.10 / average age: 47.9 ± 15, 3 years) using an indirect ELISA test and a follow-up of the fluorescence emitted after enzymatic digestion of specific peptides by proteolytic activity (chymotrypsin-like). RESULTS: The evolutionary trend proteasome subcellular is significantly linked to the rate of chymotrypsin-like activity. The entire population of 60 patients called back for a second blood test. After three months of treatment reported a significant drop in the rate and the activity of the proteasome in serum and intracellular level. CONCLUSIONS: Although the serum proteasome level is a potential new tool for the monitoring of. Patientswithliquid cancer. TRIAL REGISTRATION: retrospectively registered.
RESUMO
The aim of this work is to evaluate the antitumor effect mediated by the proteasome inhibitors of Inula viscosa extracts on skin carcinogenesis. Female Swiss albino mice were divided into five groups depending on the combination of skin cancer-inducing 7,12-dimethylbenz(a)anthracene (DMBA) and extract of Inula viscosa treatments. Histology of the affected skin and measurement of proteasome activity were performed to demonstrate the effect of Inula viscosa on mice. The identification of the molecules responsible for this inhibitory activity was carried out through the docking studies. The results showed that Inula viscosa extracts inhibit the development of papilloma in mice. Therefore, the best chemopreventive action of Inula viscosa was observed on mice in which extract treatment was performed before and after the induction of skin carcinogenesis. It was revealed that the ingestion of extracts Inula viscosa delays the formation of skin papillomas in animals and simultaneously decreases the size and number of papillomas, which is also reflected on the skin histology of the mice treated. Structure-activity relationship information obtained from component of Inula viscosa particularly tomentosin, inuviscolide, and isocosticacid demonstrated that distinct bonding modes in ß 1, ß 2, and ß 5 subunits determine its selectivity and potent inhibition for ß 5 subunit.
