Document Type: Research article
Department of Pharmacology and Toxicology, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran.
Department of Toxicology and Pharmacology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Medicinal Chemistry and Nuclear Medicine, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
The treatment of melanoma is still challenging and therefore identification of novel agents is needed for its better management. Our previous study suggested that cyclooxygenase-2 (COX-2) would be a novel target for treatment of several cancers. In the present study, we searched selective cytotoxicity and mitochondria mediated apoptosis of novel synthesized chalconeferrocenyl derivative (1-Ferrocenyl-3-(dimethylamino)-3-(4-methylsulfonylphenyl) propan-1-one) (FDMPO) as a COX-2 inhibitor on normal and melanoma cells and their mitochondria. For this purpose, we evaluated the cellar parameters such as cytotoxicity, apoptosis% versus necrosis%, activation of caspase-3 and ATP content, and also mitochondrial parameters such as reactive oxygen species formation, mitochondrial swelling, mitochondrial membrane potential decline, mitochondrial membrane integrity, and cytochrome C release. Our results showed FDMPO could selectively induce cellular and mitochondrial toxicity (up to 50 µM) on melanoma cells and mitochondria without any toxic effects on normal fibroblast and their mitochondria. Taken together, the results of this study suggest that mitochondria are a potential target for the melanoma. Selective inhibition of mitochondrial COX-2 could be an attractive therapeutic option for the effective clinical management of therapy-resistant melanoma.