Review Statins and cancers (original) (raw)

Statins and Cancer Development

Cancer Epidemiology Biomarkers & Prevention, 2005

There is epidemiologic evidence that the hydrophilic 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase inhibitor pravastatin increases the incidence of some extrahepatic cancers, although this finding has been attributed to chance. We hypothesize that pravastatin is able to promote the development of cancer by causing an induction of HMG-CoA reductase and, hence, mevalonate synthesis in extrahepatic tissues. We have shown that mevalonate, the product of HMG-CoA reductase, promotes the growth of breast cancer cells. Because there is no uptake of pravastatin by most extrahepatic cells, this statin will be unable to mitigate the increase in mevalonate synthesis in extrahepatic tissues that accompanies the decrease in circulating cholesterol caused by its inhibition of hepatic HMG-CoA reductase. (Cancer Epidemiol Biomarkers Prev

A REVIEW ARTICLE ON ANTICANCER AGENTS AND USE OF STATINS AS POTENTIAL ANTICANCER DRUG

World Journal of Pharmaceutical Science and Research, 2023

Statins have been shown to inhibit cell proliferation in vitro and tumor growth in animal models. Various studies have also shown a decreased cancer-specific mortality rate in patients who were prescribed these medications. Statins inhibit 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the rate-limiting enzyme of the mevalonate pathway. Statins induce tumour-specific apoptosis through mitochondrial apoptotic signaling pathways, which are activated by the suppression of mevalonate or geranylgeranyl pyrophosphate (GGPP) biosynthesis. The statins inhibit the production of endogenous cholesterol and may influence also cell proliferation and migration. A reduction on the cholesterol level could lead to decreased proliferation and metastasis of cancer cells. Statins had anticancer proprieties (halting cell- cycle progression in cancer cells) and reduced the risk of cancer recurrence. Many of cholesterol products resulting of synthesis pathway are used in cells proliferation. Disruption of these processes conduct to inhibition of cancer growth and metastasis, reduce angiogenesis and stimulate apoptosis. Currently, there are many ongoing clinical trials aimed at exploring the potential of statins to lower the mortality and the disease-recurrence risk. All these results are the foundation of new treatment directions in cancer therapy.

Evaluation of toxic effects of statins and their possible role in treatment of cancer

2021

Hydroxymethyl glutaryl CoA (HMG-CoA) reductase inhibitors (statins) are drugs that show hypolipidemic effect via inhibition of hydroxymethyl glutaryl CoA reductase (HMG CoA R), a rate-limiting step in the synthesis of cholesterol. The effects of statins, independent of lipid-lowering ones , are termed pleiotropic effects and these have gained importance in recent years. Potential anticancer effect, one of the pleotropic effects of statins, is remarkable. In this review we aim to summarize the possible use of statins in the treatment of cancer. Pleiotropic effects include antioxidant and antiinflammatory activities due to inhibition of new vessel formation in cancer cells, reduction of resistance to chemotherapeutic agents and inhibition of the production of reactive oxygen species (ROS) with the induction of apoptosis. The potential anticancer activity of statins against different tumor models is emphasized in vitro and in vivo conditions. For this reason, current efforts are direct...

Pleiotropic effects of statins: A focus on cancer

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2020

The statin drugs ('statins') potently inhibit hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase by competitively blocking the active site of the enzyme. Statins decrease de novo cholesterol biosynthesis and thereby reduce plasma cholesterol levels. Statins exhibit "pleiotropic" properties that are independent of their lipidlowering effects. For example, preclinical evidence suggests that statins inhibit tumor growth and induce apoptosis in specific cancer cell types. Furthermore, statins show chemo-sensitizing effects by impairing Ras family GTPase signaling. However, whether statins have clinically meaningful anti-cancer effects remains an area of active investigation. Both preclinical and clinical studies on the potential mechanisms of action of statins in several cancers have been reviewed in the literature. Considering the contradictory data on their efficacy, we present an up-to-date summary of the pleiotropic effects of statins in cancer therapy and review their impact on different malignancies. We also discuss the synergistic anti-cancer effects of statins when combined with other more conventional anti-cancer drugs to highlight areas of potential therapeutic development.

Briefly about Anticancer Properties of Statins

Biomedical Journal of Scientific & Technical Research, 2019

Statins (3-Hydroxy-3-Methylglutaryl-CoA Reductase Inhibitors) have been clinically used for the treatment of dyslipidemia / hypercholesterolemia for almost 40 years. This class of medications represents some of the most frequently prescribed drugs in the world and are the main players in pharmacologic primary and secondary prevention of atherosclerotic cardiovascular disease. Statins have gained much recent attention due to their antitumor effects. This mini review summarizes data about some potential anticancer properties of statins, putative mechanisms of their antitumor activity, and the challenges that have to be overcome in order to facilitate the introduction of these drugs in oncology practice.

Statins and Cancer Prevention—Association Does Not Mean Causation

Cancer Prevention Research

Statins are widely prescribed medications that inhibit 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG CoA) reductase and therefore reduce cholesterol synthesis. Given the key role of cholesterol in cancer, statins may therefore have anticancer activities. However, clinical studies investigating the association between statin usage and cancer development have been few and inconsistent. A recent study from Maeda-Minami and colleagues found a significant, though modest, decrease in cancer risk among statin users. However, does this finding mean statin usage directly reduces cancer risk or is merely associated with reduced cancer risk? This editorial analyzes Maeda-Minami and colleagues’ study to provide commentary on statin's proposed role in preventing cancer.See related article, p. 37

Statins: Perspectives in cancer therapeutics

Digestive and Liver Disease, 2013

Virtually any cell type in a mammalian organism uses Acetyl CoA to yield mevalonate, through the activity of the 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase enzyme and, ultimately, cholesterol. Statins have long and quite successfully been used as cholesterol lowering drugs. They reversibly inhibit the HMG-CoA reductase activity, which is rate limiting in the early steps of the cholesterol synthesis pathway. In addition to these effects, it has also been amply shown that statins may efficiently trigger cancer cell apoptosis, making them a plausible therapeutic option for the treatment of cancer. Whether statins may prevent from cancer occurrence is a matter of debate and an unanswered question, but no doubt experimental models have clearly demonstrated the potential of statins as direct cytotoxic agents, which can reduce tumor development or metastasis spreading, even more so when combined to cytotoxic drugs. Until now, however, only few data in humans support the idea that statins could rightfully enter the contingent of anticancer drugs. Nevertheless, at times where cancer cells metabolism is getting very much revisited, the mevalonate pathway has recently been reported as truly oncogenic, bringing upfront the attractive possibility to see mevalonate pathway blunting agents, such as statins, join the wealth of anticancer drugs.