Natural sesquiterpenes in the chemoprevention of biochemical and epigenetic airway changes induced by tobacco smoke exposure
Componente | Qualifica | Struttura | Categoria |
---|---|---|---|
Silvia Di Giacomo | Borsista di Ricerca | Dipartimento di Fisiologia e Farmacologia - V. Erspamer; Dip. Chimica e Tecnologie del Farmaco | Altro personale Sapienza o esterni |
Cigarette smoke (CS) is responsible for cell injury, DNA damage and inflammation at airway due to an increased intracellular oxidative stress. STAT3/ERp57 pathway has been found upregulated by CS in airways and seems responsible for oncogenic proliferation of damaged cells. Conversely, upregulating Nrf2 protein and cannabinoid system has been shown to prevent airway and lung injury. The natural sesquiterpene ß-caryophyllene (CRY) and its metabolite ß-caryophyllene oxide (CRYO) have been highlighted to possess chemopreventive properties against CS-mediated airway damage, so suggesting their possible protective role for smokers. In the present project, CRY and CRYO will be studied for their protective properties against biochemical and epigenetic changes, induced by a sample of condensed cigarette smoke (CSC) in bronchial epithelial and lung cancer cells. Also, taking into account that smoking can increase the aggressiveness of pre-existing cancers, the ability of test substances to interfere with CSC-induced migration and metastatization of lung, breast and prostate cancer cells will be studied. The possible control of CSC-mediated airway inflammation by cannabinoid system will be studied too. At last, the inhibition of class I HDAC enzyme will be evaluated as possible epigenetic chemopreventive mechanism.
Cell migration and cytotoxicity will be measured by known methods, while DNA-damage will be evaluated by micronucleus assay. Inflammation will be monitored by measuring the cytokine levels, and known cannabinoid agonists and antagonists will enclosed to evaluate the possible control by the endocannabinoid system. The modulation of the ERp57/STAT3 and Nrf2 pathways, the levels of metastatic MMP2, BIRC5 and TPX2 proteins and the activity of I HDAC enzyme will be assessed by specific proteomic and genomic analysis.
The expected results allow to acquire new knowledge on smoke-related injuries and can suggest new targets for pharmacological therapies.