Statin-Induced Inhibition of MCF-7 Breast Cancer Cell Proliferation is Related to Cell Cycle Arrest and Apoptotic and Necrotic Cell Death Mediated by an Enhanced Oxidative Stress

Abstract

Statins have antiproliferative and anti-tumoral effects in MCF-7 cells. We determined the effect of statins upon MCF-7 cell cycle, toxicity, cell death, reactive oxygen species (ROS) production and mitochondrial membrane potential. Fluvastatin, simvastatin and atorvastatin inhibited cell proliferation. Antiproliferation was associated with a decrease in the DNA synthesis and a cell cycle arrest in the G1 and G2/M phases. A loss in the mitochondrial membrane potential was observed with fluvastatin. Statins induced increase in ROS production that was associated with cell death, which was abrogated by the antioxidant NAC. Our results suggest that the cytotoxic effect observed is mediated by an oxidative stress.

Anti-cancer characteristics of mevinolin against three different solid tumor cell lines was not solely p53-dependent

“…The interference with mevalonate pathway (prenylation) was known with its complexity to be affecting several apoptotic signaling pathways 23 . Moreover, MNV and other statins have shown to affect cell viability via mixed apoptosis and necrosis pathways in the same time 24 . This explains the observed low resistant cell fractions in all cell types treated with MNV compared to DOX (Table 1).…”

“…Defective apoptosis has been reflected in the form of cell resistance to apoptotic inducing agents and, consequently, treatment failure. MVN has been suggested to induce cell death via multiple apoptotic 13 , necrotic 24 and autophagic pathways 14 . In the current work, MCF-7 seemed to undergo apoptosis by the p53-dependent pathway; however both Bcl 2 and BAX were not significantly affected (Figure 2).…”

Is immunity a mechanism contributing to statin-induced diabetes?

“…Increased production of mitochondrial reactive oxygen species (mtROS), altered mitochondrial membrane potential and decreased intracellular ATP levels have been observed with concentrations of statin as low as 1 mM. [68][69][70][71][72] Statins have also been shown to promote a modest increase in cellular ROS and an increase of ATP release in THP-1 monocytes. 56 Statininduced IL-1b production was also shown to be dependent on P2X purinoceptor 7 (P2X7) activation.…”

HMG-CoA reductase regulates CCL17-induced colon cancer cell migration via geranylgeranylation and RhoA activation

“…Although statins are mainly used to regulate cholesterol synthesis in patients with increased risk of cardiovascular complications [11], the literature suggests that statins, such as simvastatin, also exert anti-tumor effects, such as induction of cell cycle arrest [12] and apoptosis [13]. Statins inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, which is the rate-limiting enzyme in the formation of mevalonate [14].…”