TARGETING A SOLITARY FIBROUS TUMOR CELL LINE USING A NOVEL NANOMICELLE FORMULATION TO ENHANCE CURCUMIN ANTITUMOR ACTIVITY

Various evidence has shown that curcumin, a natural compound, can induce increased sensitivity to chemotherapy, inhibit tumor growth, metastasis formation and Epithelial-Mesenchymal Transition (EMT). A solitary fibrous tumor (SFT) cell line treated with curcumin (50μMol) showed a decreased expression of EMT markers. However, this concentration is incompatible with its in vivo use. Therefore, it is thought of use curcumin encapsulated by nanomicelles that can deliver curcumin directly to the cells. Nanomicelle treatments, named C16-DAPMA, C16-SPD and C16-SPM, analyzed by means MTT, showed their cytotoxic potential using a significantly lower curcumin concentrations (500nM, 1μM). Moreover, performing biochemical analyses, it was possible to detect a reduction in the expression of EMT-associated markers, particularly significant after treatment with C16-SPD. In addition, invasion assay shed light on the invasive potential of SFT cells that, after treatment with nanomicelles, resulted significantly lower than the untreated control. Due to its low toxicity, curcumin could be administered in combination with other drugs, such as histonedeacetylase inhibitors (HDACi), which can inhibit migration and tumor growth. Combinations with HDACis and nanomicelles resulted in a decreased expression of HDAC2, especially after treatment with C16-DAPMA, while C16-SPD significantly reduced the expression of metalloproteinase 2(MMP2). In addition, immunofluorescence analysis after HDACi treatments, revealed a loss of spindle-fused SFT tumor cell structure in favor of a more epithelioid-like. Photodynamic Therapy (PDT) is an innovative minimally invasive technique, which is not subject to resistance, easily manageable, selective, does not involve systemic toxicity such as standard chemotherapy and does not induce resistance phenomena. Recent studies also report that the cytotoxic effect obtained using low concentrations of curcumin, administered in combination with blue light (laser) on tumor cell lines, was particularly significant using nanomicelle-encapsulated with curcumin. In line with studies already published, preliminary MTT analyses, performed on SFT cells irradiated with blue laser and treated with nanomicelles loaded with curcumin, showed a significant reduction in tumor cell viability.