Simvastatin impairs murine melanoma growth

Abstract

BackgroundStatins induces cell cycle arrest, apoptosis, reduction of angiogenic factors, inhibition of the endothelial growth factor, impairing tissue adhesion and attenuation of the resistance mechanisms. The aim of this study was evaluate the anti-tumoral activity of simvastatin in a B16F10 melanoma-mouse model.MethodsMelanoma cells were treated with different concentrations of simvastatin and assessed by viability methods. Melanoma cells (5 × 104) were implanted in two month old C57Bl6/J mice. Around 7 days after cells injection, the oral treatments were started with simvastatin (5 mg/kg/day, p.o.). Tumor size, hematological and biochemical analyses were evaluated.ResultsSimvastatin at a concentration of 0.8 μM, 1.2 μM and 1.6 μM had toxic effect. Concentration of 1.6 μM induced a massive death in the first 24 h of incubation. Simvastatin at 0.8 μM induces early cell cycle arrest in G0/G1, followed by increase of hypodiploidy. Tumor size were evaluated and the difference of treated group and control, after ten days, demonstrates that simvastatin inhibited the tumor expansion in 68%.ConclusionSimvastatin at 1.6 μM, presented cytototoxicity after 72 h of treatment, with an intense death. In vivo, simvastatin being potentially useful as an antiproliferative drug, with an impairment of growth after ten days.

Regulation of apoptosis in human melanoma and neuroblastoma cells by statins, sodium arsenite and TRAIL: a role of combined treatment versus monotherapy

“…Animal experiments with the B16F10 mouse melanoma model exhibited a suppression of tumor growth by treatment with 1.6 μM simvastatin [45]. However, a regular statin treatment of patients for the control of cholesterol levels appears does not display a pronounced anti-melanoma protection [46, 47].…”

Simvastatin Protects Osteoblasts from the Deleterious Effects of the Liquid Milieu of Multiple Myeloma

“…Simvastatin was activated by dissolving in 1.8 mL of ethanol, added to 19 mL of sodium hydroxide (NaOH; 0.1 M) and then incubated for 40 minutes at 40°C to convert the lactone. To adjust the pH to 7.4, hydrochloric acid (HCl; 0.1 M) was added (8). Associations between the supernatant (S) and multiple myeloma simvastatin (Sim) were held in the proportions: 5 µL of S with 0.8 µM Sim (S1 + Sim1), 15 µL of S with 1.2 µM Sim (S2 + Sim2), 30 µL of S with 1.6 µM of Sim (S3 + Sim3), 0.8 µM of Sim with 30 µL of S (Sim1 + S3) and 5 µL of S with 1.6 µM of Sim (S1 + Sim3).…”

Pravastatin induces cell cycle arrest and decreased production of VEGF and bFGF in multiple myeloma cell line

“…These effects have been tested in different cancers such as melanoma (Favero et al, 2010), thyroid cancer (Zhong et al, 2011) osteosarcoma (Tsubaki et al, 2011), hepatocellular carcinoma (Tijeras-Raballand et al, 2010). Additionally, several studies have shown that statins reduce cell proliferation in hematopoietic malignancies such as chronic lymphocytic leukemia (Podhorecka et al, 2010), acute promyelocytic leukemia NB4 (Sassano et al, 2007) and MM (Otsuki et al, 2004).…”