Cytotoxicity of lipophilic statins depends on their combined actions on HIF-1α expression and redox status in B16.F10 melanoma cells
| Autor: | Manuela Banciu, Emilia Licarete, Flavia B. Cristian, Marius Costel Alupei |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Simvastatin
Cancer Research Statin Cell Survival medicine.drug_class Melanoma Experimental Apoptosis Pharmacology Mice Necrosis chemistry.chemical_compound Cell Line Tumor medicine Animals Cytotoxic T cell Pharmacology (medical) Propidium iodide Cytotoxicity Cell Proliferation Pravastatin Chemistry Cell growth nutritional and metabolic diseases Hypoxia-Inducible Factor 1 alpha Subunit Oxidative Stress Oncology Cell culture lipids (amino acids peptides and proteins) Lovastatin Hydroxymethylglutaryl-CoA Reductase Inhibitors Oxidation-Reduction medicine.drug |
| Zdroj: | Anti-Cancer Drugs. 25:393-405 |
| ISSN: | 0959-4973 |
| DOI: | 10.1097/cad.0000000000000065 |
| Popis: | Statins, as inhibitors of de-novo synthesis of cholesterol, exert cytotoxic actions on tumor cells. Despite the increasing data on the antitumoral activities of statins, their complete mechanisms of action still remain obscure. Therefore, the present study aims to investigate the mechanisms of lipophilic statin-induced cytotoxicity on B16.F10 murine melanoma cells in vitro. In-vitro effects of two lipophilic statins, simvastatin and lovastatin, and a hydrophilic statin, pravastatin, were investigated with respect to B16.F10 murine melanoma cell proliferation and viability. Our results show that only lipophilic statins exerted strong cytotoxic effects on B16.F10 melanoma cells. To gain further evidence on the pleiotropic effects of statins responsible for their cytotoxicity in B16.F10 cells, we have assessed their proapoptotic effects by Annexin V-fluorescein isothiocyanate/propidium iodide staining and measured tumor cell production of the hypoxia-inducible factor 1α by western blot analysis, nonenzymatic antioxidant levels by an antioxidant colorimetric assay, and superoxide dismutase activity through an indirect method on the basis of inhibition of xanthine oxidase activity. Protein array was also used to assess angiogenic/inflammatory protein production in B16.F10 cells. Our results pointed out that the cytotoxic actions exerted by lipophilic statins were mainly based on the suppressive actions of these drugs on hypoxia-inducible factor 1α expression and nonenzymatic antioxidant levels, as well as because of the inhibition of superoxide dismutase activity in B16.F10 melanoma cells. In addition, the reduction in the angiogenic/inflammatory capacity of tumor cells induced by lipophilic statins can strengthen and support their cytotoxicity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|