Statins inhibit the proliferation and induce cell death of human papilloma virus positive and negative cervical cancer cells
Loading...
Authors
Crescencio, María Elena
Rodríguez, Emma
Páez, Araceli
Masso, Felipe A.
Montaño, Luis F.
López-Marure, Rebeca
Issue Date
2009-12
Type
Article
Language
en_US
Keywords
Statins , Cell Cycle , Cell Death , Proliferation , Cervical Cancer , Mevalonate Pathway , Oxidative Stress , Human Papilloma Virus
Alternative Title
Abstract
Statins, competitive inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, have anti-tumoral effects on multiple cancer types; however, little is known about their effect on cervical cancer. We evaluated the effect on proliferation, cell cycle, oxidative stress and cell death of three statins on CaSki, HeLa (HPV+) and ViBo (HPV−) cervical cancer cell lines. Cell proliferation was assayed by crystal violet staining, cell cycle by flow cytometry and cell death by annexin-V staining. Reactive oxygen species (ROS) production was evaluated by the oxidation of 2,7-dichlorofluorescein diacetate and nitrite concentration (an indirect measure of nitric oxide (NO) production), by the Griess reaction. Inhibition of cell proliferation by atorvastatin, fluvastatin and simvastatin was dose-dependent. ViBo cells were the most responsive. Statins did not affect the cell cycle, instead they induced cell death. The antiproliferative effect in ViBo cells was completely inhibited with mevalonate, farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP) treatments. In contrast, cell proliferation of CaSki and HeLa cells was partially (33%) rescued with these intermediates. The three statins increased ROS and nitrite production, mainly in the ViBo cell line. These results suggest that statins exert anti-tumoral effects on cervical cancer through inhibition of cell proliferation and induction of cell death and oxidative stress. Statins could be an aid in the treatment of cervical cancer, especially in HPV− tumors.
Description
Citation
Crescencio, M. E., Rodríguez, E., Páez, A., Masso, F. A., Montaño, L. F., & López-Marure, R. (2009). Statins inhibit the proliferation and induce cell death of human papilloma virus positive and negative cervical cancer cells. International journal of biomedical science : IJBS, 5(4), 411–420.
Publisher
International Journal of Biomedical Science : IJBS