Antiproliferative effect and apoptosis induction in melanoma treatment by boron neutron capture therapy (BCNT)

Full text: Introduction: Boron neutron capture therapy (BNCT) is an experimental radiotherapy where a compound having 10B is administered to cancer patients and is accumulated in tumor tissues. Thus, the tumor is irradiated with thermal neutrons, 10B absorbs and destroys them, producing alpha radiation. Boronophenylalanine (BPA) is the agent responsible for delivering boron to the tumor tissue. After BPA administration, BNCT is used as a localized radiotherapy for many tumors treatment, mainly melanoma, which has a high mortality rate among all types of tumors. The aim of this study was to evaluate in vitro antiproliferative and antitumor effects of BNCT application in human melanoma treatment. Materials and Methods: MEWO cells (human melanoma) were cultured and treated with different concentrations of BPA (8.36 to 0.52 mg/ml). After 90 minutes, they were irradiated with thermal neutron flux up to a dose of 8.4 Gy. The parameters analyzed were free radical production, cell cycle progression, cell death signaling pathways, cycling D1, caspase-3 and extracellular matrix synthesis produced, beyond the mitochondrial electric potential analysis. Results: After BNCT treatment, MEWO cells showed an amount of free radical increase about 10 times. Still, there was a significant decrease of cyclin D1, G0/G1 proliferation, synthesis and G2/M cell cycle phases. BNCT induced a mitochondrial electrical potential decrease, as well as fibrillar proteins of extracellular matrix. BNCT had a significant number of dead cell increase, mainly by necrosis. However, BNCT induced phosphorylated caspase 3 increase. Discussion/Conclusion: BNCT induced cell death increase by necrosis, mitochondrial electric potential decrease and free radical production increase. BNCT is cytotoxic to melanoma cells. Besides necrosis, phosphorylated caspase 3 increase was observed, accompanied by a proliferative response decrease regulated by the G1/S checkpoint and matrix extracellular synthesis reduction. These results corroborate with cyclin D1 marker decrease. Thus, BNCT is a modality with high specificity for melanoma treatment. (author)