Mecanismo de ação da cedrelona na morte celular programada de células de câncer de mama

Abstract

Cancer is among the leading causes of death in the world and breast cancer is the type of cancer that affects more women. The treatment of this disorder requires a careful selection of one or more methods of intervention. The majority of drugs currently used in chemotherapy causes DNA damage in tumor cells and also in normal cells, therefore the development of new chemotherapeutic agents is challenging, since these chemotherapeutic agents should be able to kill or inhibit the growth only of tumor cells. From ancient times until today plants and their products have been used for the treatment of diseases, thus the natural compounds may provide new opportunities for the development of cancer drugs. Cedrelone is an isolated limonoid from methanol extract of Trichilia catigua aryl, a native Brazilian plant that grows abundantly in various regions of the country and is popularly known as "cedrinho", "catuaba" or "catiguá". Studies have shown that cedrelone has insecticidal and antifungal activity and previous studies performed by our research group have demonstrated that cedrelone is able to inhibit proliferation, colony formation, cell adhesion, migration, invasion and moreover, to induce apoptosis in triple negative breast cancer cells from the line MDAMB- 231. Therefore, the aim of this study was to identify the mechanism of action of cedrelone in triple negative breast tumor cells, MDA-MB-231, through cedrelone analysis, and through cell morphology assay, colony formation, apoptosis assays such as DNA fragmentation and nuclear fragmentation, cell cycle, qRT-PCR and western blotting. The results demonstrate that cedrelone has an affinity for biological membranes and no antioxidant activity. Furthermore, cedrelone is capable of inducing morphological changes, reduce the number and size of colonies and induce apoptosis by increasing the gene expression of pro-apoptotic protein Bax and decreasing gene expression of anti-apoptotic Bcl-2 in MDA-MB-231. These results indicate that cedrelone has immense potential in cancer therapy based on their antiproliferative and apoptosis inducing effects.