The effect of statins on cancer cells—review

Abstract

Statins [3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase, abbreviated HMGCR) inhibitors], are well-known cholesterol-depleting agents. Since the early 1990 s, it has been known that statins could be successfully used in cancer therapy, but the exact mechanism(s) of statin activity remains unclear and is now an extensive focus of investigation. So far, it was proven that there are several mechanisms that are activated by statins in cancer cells; some of them are leading to cell death. Statins exert different effects depending on cell line, statin concentration, duration of exposure of cells to statins, and the type of statin being used. It was shown that statins may inhibit the cell cycle by influence on both expression and activity of proteins involved in cell-cycle progression such as cyclins, cyclin-dependent kinases (CDK), and/or inhibitors of CDK. Also, statins may induce apoptosis by both intrinsic and extrinsic pathways. Statin treatment may lead to changes in molecular pathways dependent on the EGF receptor, mainly via inhibition of isoprenoid synthesis. By inhibition of the synthesis of cholesterol, statins may destabilize the cell membrane. Moreover, statins may change the arrangement of transporter OATP1, the localization of HMGCR, and could induce conformational changes in GLUT proteins. In this review, we have tried to gather and compare most of the recent outcomes of the research in this field. We have also attempted to explain why hydrophilic statins are less effective than hydrophobic statins. Finally, we have gathered results from in vivo experiments, presenting the use of statins in combined therapies and discussed a number of molecular targets that could serve as biomarkers predisposing to statin therapy.

The p53 family orchestrates the regulation of metabolism: physiological regulation and implications for cancer therapy

“…Intriguingly, part of this anticancer effect can be attributed to the capability of metformin to increase the levels of TAp63, in turn promoting the TAp63-mediated induction of genes crucial for both metabolic regulation and tumour suppression, such as AMPKα2 , LKB1 , and SIRT1 (Su et al , 2012). Another promising anticancer strategy is represented by the usage of statins (Matusewicz et al , 2015) that have been proved to limit the oncogenic properties of mutant p53 (Freed-Pastor et al , 2012). Given that one of the main features of mutant p53 is to sequester TAp63 and TAp73, it can be hypothesised that part of the tumour suppressive activities associated with statins might be achieved by unleashing these two transcription factors.…”

Inverse association between statin use and head and neck cancer: Population‐based case‐control study in Han population

“…Recently, increasing biological evidence has indicated that statins not only decrease plasma cholesterol, but also have some antitumor effects, such as inhibiting cell proliferation, suppressing angiogenesis, and triggering cell apoptosis . Therefore, increasing numbers of investigators have considered that statins may be prospective agents for cancer prevention and treatment …”

“…[5][6][7][8][9] Therefore, increasing numbers of investigators have considered that statins may be prospective agents for cancer prevention and treatment. 10 Head and neck cancers are the sixth most prevalent type of malignancy worldwide. 11 Over 90% of head and neck cancer cases are categorized as squamous cell carcinomas (SCCs), and this disease frequently occurs in the oral cavity, pharynx, larynx, nasal cavity, paranasal sinuses, and so forth.…”

pPeOp from Omphalia lapidescens Schroet induces cell cycle arrest and inhibits the migration of MC-4 gastric tumor cells

“…An uncontrolled cell cycle is closely associated with tumor occurrence, development and malignancy (28,29). Once cell proliferation or inappropriate cell death occurs, it typically results in a tumor, and it has been demonstrated that the regulation of the cell cycle is an important mechanism in tumorigenesis.…”