Effects of statins on brain tumors: a review

Afshari, Amir R.; Mollazadeh, Hamid; Henney, Neil C.; Jamialahmadi, Tannaz; Sahebkar, Amirhossein

doi:10.1016/j.semcancer.2020.08.002

Cited by 64 publications

(44 citation statements)

References 232 publications

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“…Induction of apoptosis in tumor cells is considered to act as a protective mechanism that inhibits neoplastic development by eliminating the cells that have been improperly stimulated for proliferation. 31 , 32 LY294002 (2-4-morpholinyl-8-phenlchromone) is a chemical inhibitor of PI3K that is used extensively to study the role of the PI3K/Akt pathway in normal and transformed cells. 33 , 34 Our results confirmed that β-mangostin with PI3K broad-spectrum inhibitor LY294002 could further decrease the phosphorylation of Akt in C6 cells.…”

Section: Discussionmentioning

confidence: 99%

<p>Cytotoxic and Antiproliferative Effects of β-Mangostin on Rat C6 Glioma Cells Depend on Oxidative Stress Induction via PI3K/AKT/mTOR Pathway Inhibition</p>

Chen

et al. 2020

DDDT

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Background: Glioma is the most common malignant tumor of the nervous system, which accounts for more than 45% of central nervous system tumors and seriously threatens our health. Because of high mortality rate, limitations, and many complications of traditional treatment methods, new treatment methods are urgently needed. β-Mangostin is a natural compound derived from the fruit of Garcinia mangostana L. and it has anticancer activity in several types of cancer cells. However, the antitumor effect of β-mangostin in glioma has not been clarified. Hence, this study aimed to investigate its therapeutic effects on gliomas. Materials and Methods: To study the effect of β-mangostin on glioma cells, cell viability assay, reactive oxygen species production, cell cycle, apoptosis, and mitochondrial membrane potential were evaluated in the C6 cell line in vitro. Immunofluorescence and Western blotting were used to analyze protein expression and phosphorylation to study its mechanism of action. A subcutaneous xenograft model was used to investigate the effect of β-mangostin on tumorigenesis in vivo. Results: We found that β-mangostin can inhibit glioma cell growth and induce oxidative damage in vitro. In addition, it reduces the phosphorylated form levels of PI3K, AKT and mTOR. Furthermore, the phosphorylated form levels of PI3K, AKT and mTOR were increased after the PI3K inhibitor was added. In vivo experiments showed that βmangostin can inhibit tumor growth as shown by its reduced size and weight. Conclusion: This study suggests that β-mangostin can inhibit cell proliferation and induce oxidative damage in cells. It is the first study to demonstrate that β-mangostin induces oxidative damage in glioma cells by inhibiting the PI3K/AKT/mTOR signaling pathway.

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Section: Discussionmentioning

confidence: 99%

<p>Cytotoxic and Antiproliferative Effects of β-Mangostin on Rat C6 Glioma Cells Depend on Oxidative Stress Induction via PI3K/AKT/mTOR Pathway Inhibition</p>

Chen

et al. 2020

DDDT

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“…Moreover, cholesterol is not only a final product of this biochemical pathway but also itself an intermediate for many other compounds, such as corticosteroids, bile acids, and vitamin D 15 . This explains why statins pharmacodynamically exert pleiotropic effects, 16–21 which are responsible for both beneficial and adverse consequences during treatment. Apart from their cholesterol‐lowering effect, statins are known to contribute to stabilization of atherosclerotic plaques, 22 improvement of endothelial dysfunction, 23 and immunomodulation and show anti‐inflammatory, 24 antioxidant, and anti‐thrombotic effects 25 .…”

Section: Introductionmentioning

confidence: 99%

Effects of statins on mitochondrial pathways

Mollazadeh

Tavana

Fanni

et al. 2021

J cachexia sarcopenia muscle

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147

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Statins are a family of drugs that are used for treating hyperlipidaemia with a recognized capacity to prevent cardiovascular disease events. They inhibit β-hydroxy β-methylglutaryl-coenzyme A reductase, i.e. the rate-limiting enzyme in mevalonate pathway, reduce endogenous cholesterol synthesis, and increase low-density lipoprotein clearance by promoting low-density lipoprotein receptor expression mainly in the hepatocytes. Statins have pleiotropic effects including stabilization of atherosclerotic plaques, immunomodulation, anti-inflammatory properties, improvement of endothelial function, antioxidant, and anti-thrombotic action. Despite all beneficial effects, statins may elicit adverse reactions such as myopathy. Studies have shown that mitochondria play an important role in statin-induced myopathies. In this review, we aim to report the mechanisms of action of statins on mitochondrial function. Results have shown that statins have several effects on mitochondria including reduction of coenzyme Q10 level, inhibition of respiratory chain complexes, induction of mitochondrial apoptosis, dysregulation of Ca 2+ metabolism, and carnitine palmitoyltransferase-2 expression. The use of statins has been associated with the onset of additional pathological conditions like diabetes and dementia as a result of interference with mitochondrial pathways by various mechanisms, such as reduction in mitochondrial oxidative phosphorylation, increase in oxidative stress, decrease in uncoupling protein 3 concentration, and interference in amyloid-β metabolism. Overall, data reported in this review suggest that statins may have major effects on mitochondrial function, and some of their adverse effects might be mediated through mitochondrial pathways.

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“…Another strategy to either control foam cell formation or increase the clearance of foam cells is statin therapy. Statins have been extensively investigated in patients with cardiovascular disease due to their numerous pleiotropic effects such as reducing oxidative stress, enhancing plaque stability and exerting anti-inflammatory effects [ 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 ]. Following foam cell formation, the foam cells take on a profibrotic phenotype.…”

Section: Foam Cells As Therapeutic Targets In Atherosclerosismentioning

confidence: 99%

Foam Cells as Therapeutic Targets in Atherosclerosis with a Focus on the Regulatory Roles of Non-Coding RNAs

Javadifar

Rastgoo

Banach

et al. 2021

IJMS

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Atherosclerosis is a major cause of human cardiovascular disease, which is the leading cause of mortality around the world. Various physiological and pathological processes are involved, including chronic inflammation, dysregulation of lipid metabolism, development of an environment characterized by oxidative stress and improper immune responses. Accordingly, the expansion of novel targets for the treatment of atherosclerosis is necessary. In this study, we focus on the role of foam cells in the development of atherosclerosis. The specific therapeutic goals associated with each stage in the formation of foam cells and the development of atherosclerosis will be considered. Processing and metabolism of cholesterol in the macrophage is one of the main steps in foam cell formation. Cholesterol processing involves lipid uptake, cholesterol esterification and cholesterol efflux, which ultimately leads to cholesterol equilibrium in the macrophage. Recently, many preclinical studies have appeared concerning the role of non-encoding RNAs in the formation of atherosclerotic lesions. Non-encoding RNAs, especially microRNAs, are considered regulators of lipid metabolism by affecting the expression of genes involved in the uptake (e.g., CD36 and LOX1) esterification (ACAT1) and efflux (ABCA1, ABCG1) of cholesterol. They are also able to regulate inflammatory pathways, produce cytokines and mediate foam cell apoptosis. We have reviewed important preclinical evidence of their therapeutic targeting in atherosclerosis, with a special focus on foam cell formation.

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Effects of statins on brain tumors: a review

Cited by 64 publications

References 232 publications

<p>Cytotoxic and Antiproliferative Effects of β-Mangostin on Rat C6 Glioma Cells Depend on Oxidative Stress Induction via PI3K/AKT/mTOR Pathway Inhibition</p>

<p>Cytotoxic and Antiproliferative Effects of β-Mangostin on Rat C6 Glioma Cells Depend on Oxidative Stress Induction via PI3K/AKT/mTOR Pathway Inhibition</p>

Effects of statins on mitochondrial pathways

Foam Cells as Therapeutic Targets in Atherosclerosis with a Focus on the Regulatory Roles of Non-Coding RNAs

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