Avaliação do efeito antineoplásico da curcumina em células metastáticas de melanoma cutâneo

Abstract

Cutaneous melanoma (CM) is an aggressive type of cancer in which mortality rates are high. Even with the inclusion of new therapies, some patients do not show complete response to treatment, reducing survival. In this sense, it is important to study new alternatives for the treatment of this disease. Natural compounds have shown promising results in relation to this type of cancer, among these compounds is curcumin, which in other studies showed anti-inflammatory, antioxidant, and antitumor activity. Moreover, in relation to the new therapeutic targets is the purinergic system that encompasses an extracellular signaling network that is closely related to tumor progression and still with respect to new therapeutic targets another component to be highlighted is the NLRP3 inflammasome that is responsible for triggering the inflammatory response and in MC is related to resistance to therapies and metastasis. The aim of this work is to evaluate the effect of curcumin on metastatic cutaneous melanoma cell line, SK-Mel-28. Cells were cultured under optimal conditions and treated with different concentrations (0.1 uM to 100 uM) of curcumin for 6 or 24 hours. Subsequently cell viability was assessed, along with apoptotic index, caspase-3, cell migration, redox status, components of the purinergic system and NLRP3 inflammasome. Curcumin showed antitumor effect at all tested concentrations after 6 hours of treatment and at concentrations of 10 uM and 100 uM after 24 hours of treatment. In addition, it induced apoptosis and positively regulated caspase-3 activity and gene expression. In order to know the biochemical pathways of action, we observed exacerbation of ROS, reduction of immunosuppression by decreasing the activity and gene and protein expression of CD39 and CD73 ectonucleotidases, and negative regulation of the NLRP3 inflammasome. Demonstrating that curcumin acts in various ways on MC and is a promising agent to be tested in clinical trials involving the treatment of metastatic cutaneous melanoma.