Antitumor Potential of S-Nitrosothiol-Containing Polymeric Nanoparticles against Melanoma

作者：Ferraz Leticia S; Watashi Carolina M; Colturato Kido Carina; Pelegrino Milena T; Paredes Gamero Edgar J; Weller Richard B; Seabra Amedea B; Rodrigues Tiago

来源：Molecular Pharmaceutics, 2018, 15(3): 1160-1168.

DOI：10.1021/acs.molpharmaceut.7b01001

• cytotoxicity
• melanoma
• nanoparticles
• nitric oxide
• S-nitrosothiol

Melanoma is a malignant proliferative disease originated from melanocyte transformations, which are characterized by a high metastatic rate and mortality. Advances in Nanotechnology have provided useful new approaches and tools for antitumor chemotherapy. The aim of this study was to investigate the molecular mechanisms underlying chitosan nanoparticles containing S-nitrosomercaptosuccinic acid (S-nitroso-MSA-CS) induced cytotoxicity in melanoma cells. S-Nitroso-MSA-CS induced concentration dependent cell death against B16-F10 tumor cells, whereas non-nitroso nanopartides (CS or MSA-CS) did not induce significant cytotoxicity. Additionally, melanoma cells were more sensitive to cell death than normal melanocytes. S-Nitroso-MSA-CS-induced cytotoxicity exhibited features of caspase-dependent apoptosis, and it was associated with oxidative stress, characterized by increased mitochondrial superoxide production and oxidation of protein thiol groups. In addition, tyrosine nitration and cysteine S-nitrosylation of amino acid residues in cellular proteins were observed. The potential use of these nanoparticles in antitumor chemotherapy of melanoma is discussed.

• 出版日期2018-3