Current perspectives on statins as potential anti-cancer therapeutics: clinical outcomes and underlying molecular mechanisms

Abstract

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. However, there is no consensus on the molecular targets of statins for their anti-cancer effects. Several studies have been conducted to further assess the association between statin use and mortality in different types of cancer. In this review, current perspectives on clinical significance of statins in prevention and treatment of various types of cancers and proposed mechanisms are discussed.

Statin and the risk of hepatocellular carcinoma in patients with hepatitis B virus or hepatitis C virus infection: a meta-analysis

“…Statins, also known as 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase inhibitors, are a category of cholesterol-lowering medications which have become the mainstays for the primary and secondary prevention of cardiovascular diseases [8]. Moreover, increasing evidence demonstrates the potential pleiotropy of statins, such as anti-inflammation, immunomodulation, proapoptosis, anti-proliferation, and anti-invasion, all of which have been implicated in carcinogenesis and metastasis [9,10]. Therefore, statins have been suggested as anticancer agents [11].…”

Statin use and the prognosis of patients with hepatocellular carcinoma: a meta-analysis

“…Statins, also known as 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase inhibitors, are a category of cholesterol-lowering medications that have become mainstays for the primary and secondary prevention of cardiovascular diseases [5]. Moreover, the potential pleiotropy of statins besides their cholesterol-lowering effect has been revealed, such as anti-inflammation, immunomodulation, pro-apoptosis, anti-proliferation, and anti-invasion, all of which are implicated in carcinogenesis and metastasis [6,7]. Accordingly, statins have been proposed to confer anticancer effect, and use of statin may reduce cancer risk [8].…”

Network-Based Drug Discovery Identifies Statins as a Repurposing Agent to Improve Activity of Current Therapies in Chronic Lymphocytic Leukemia.

“…It has also been reported in lymphoma cells that statins induced apoptosis by promoting ROS generation and regulating Akt, Erk and p38 signals via suppression of mevalonate pathway [37]. Furthermore, isoprenoid intermediates of mevalonate pathway might in uence the expression of genes participating in the regulation of cell proliferation and transformation [29]. Simvastatin also targets the integrin LFA-1 [19].…”

“…Statins show numerous pleiotropic effects including anti-in ammatory, anti-angiogenic, anti-oxidant and anticancer activities [27]. Multiple pleiotropic anti-cancer effects were observed such as induction of cell cycle arrest, apoptosis, inhibition of migration, invasion, metastasis and angiogenesis [28,29] and particularly, a cytotoxic effect was reported in hematological malignancies [30,31]. Epidemiologic studies suggest improved outcomes in some hematological malignancies in the statins users [32,33].…”