Selected Statins as Dual Antiproliferative-Antiinflammatory Compounds (original) (raw)
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The Effect of Statins in Combination with Chemotherapy on Colon Cancer Cell Lines
Journal of Babol University of Medical Sciences, 2022
Background and Objective: Considering the anti-cancer effects of statins on colon cancer previously reported in epidemiological studies and uncertainty about the mechanisms of action, this study was performed to investigate the effect of statins in combination with chemotherapy on colon cancer cell lines. Methods: The present study, which is a laboratory study, was performed on HT-29 cell line as colon cancer cell line and normal HFF cell line. After cell culture, atorvastatin at doses of 15 and 30 μM, rosuvastatin at doses of 30 and 60 μM, simvastatin at doses of 10 and 20 μM and 5-fluorouracil (5-FU) at 20 μg/ml were used for interventions in this study. Interventions were performed alone and in combination. Finally, MTT test was performed to evaluate cell viability. Findings: Mean cell viability in simvastatin (20 μM) and simvastatin (20 μM)+5-FU (20 μg/ml) on colorectal cancer cell lines was 58.46±7.58 and 55.73±15.33 (p=0.999), respectively, in rosuvastatin (30 μM) and rosuvastatin (30 μM)+5-FU (20 μg/ml) was 91.63±10.3 and 56.2±10.27 (p=0.026), respectively, and in atorvastatin (30 μM) and atorvastatin (30 μM)+5-FU (20 μg/ml) was 82.3±26.9 and 52.16±9.49 (p=0.24), respectively. Conclusion: The evaluation of cell proliferation showed that the addition of rosuvastatin to standard chemotherapy, unlike atorvastatin and simvastatin, had an increasing effect on cytotoxicity.
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: 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.
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...
PLoS ONE, 2011
3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) inhibitors, commonly known as statins, may possess cancer preventive and therapeutic properties. Statins are effective suppressors of cholesterol synthesis with a well-established riskbenefit ratio in cardiovascular disease prevention. Mechanistically, targeting HMGCR activity primarily influences cholesterol biosynthesis and prenylation of signaling proteins. Pravastatin is a hydrophilic statin that is selectively taken up by a sodium-independent organic anion transporter protein-1B1 (OATP1B1) exclusively expressed in liver. Simvastatin is a hydrophobic statin that enters cells by other mechanisms. Poorly-differentiated and well-differentiated cancer cell lines were selected from various tissues and examined for their response to these two statins. Simvastatin inhibited the growth of most tumor cell lines more effectively than pravastatin in a dose dependent manner. Poorly-differentiated cancer cells were generally more responsive to simvastatin than well-differentiated cancer cells, and the levels of HMGCR expression did not consistently correlate with response to statin treatment. Pravastatin had a significant effect on normal hepatocytes due to facilitated uptake and a lesser effect on prostate PC3 and colon Caco-2 cancer cells since the OATP1B1 mRNA and protein were only found in the normal liver and hepatocytes. The inhibition of cell growth was accompanied by distinct alterations in mitochondrial networks and dramatic changes in cellular morphology related to cofilin regulation and loss of p-caveolin. Both statins, hydrophilic pravastatin and hypdrophobic simvastatin caused redistribution of OATP1B1 and HMGCR to perinuclear sites. In conclusion, the specific chemical properties of different classes of statins dictate mechanistic properties which may be relevant when evaluating biological responses to statins.
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.
Anti-Tumor Effects of Simvastatin on UMR-106 Osteosarcoma Cell Line
2011
Statins have been widely used for the treatment of hypercholesterolemia and other cardiovascular diseases. Recently, statins have been studied for their apoptotic effects which make them relevant for cancer prevention and treatment; however, their exact mechanisms of action are still unclear. In this study, we used malignant UMR-106 osteosarcoma cells and normal HTR8/SVneo extravillous trophoblast cells, and found that simvastatin decreases cell viability, in a dose and time-dependent manner in both cell types. In addition, 10 µM simvastatin was able to induce apoptosis in trophoblast cells as evaluated by FACS analysis. Finally, proteomic analysis of protein expression suggests a specific regulatory mechanism that could explain some of the anticancer effects of this statin.
Journal of thee Medical Sciences (Berkala Ilmu Kedokteran)
Statins is HMG-CoA inhibitors which used for decreasing plasma cholesterol levels and preventing coronary artery disease. Preclinical and clinical studies showed that statin could decrease the risk of cancer. This study was performed to evaluate the cytotoxic activity of simvastatin on T47D breast cancer cell lines and its effect in cyclin D 1 expression and apoptosis. This was quasi experiment using post test with non-equivalent control group design. Simvastatin cytotoxic activity was evaluated using MTT assay. Furthermore, the effect of simvastatin on cyclin D 1 expression and apoptosis were evaluated using flow cytometry using antibody monoclonal anti-cyclin D 1 and annexin V-Pi, respectively. The results showed that simvastatin had cytotoxic activity on T47D breast cancer cell lines with an IC 50 value of 25.25 ± 1.61 µg/mL. Moreover, simvastatin in concentration range from 6.31 to 50.5 µg/mL decreased the cyclin D1 expression with an EC 50 value of 18.96±4.42 µg/mL and induced apoptosis with an EC 50 value of 26.96 ± 6.05 µg/mL. In conclusion, simvastatin inhibits T47D breast cancer cell growth through reduction of cyclin D 1 expression and induction of apoptosis. ABSTRAK Statin (HMG-CoA inhibitor) merupakan golongan obat yang digunakan untuk menurunkan kadar kolesterol plasma dan untuk mencegah jantung koroner. Penelitian praklinik dan klinik menunjukkan bahwa terapi statin dapat menurunkan risiko terjadinya kanker. Penelitian ini bertujuan mengkaji aktivitas sitotoksik simvastatin terhadap kultur sel kanker payudara T47D dan efeknya terhadap ekspresi cyclin D 1 dan apoptosis. Jenis penelitian ini adalah eksperimenal semu dengan rancangan post test with non equivalent control group. Aktivitas sitotoksi simvastatin diuji dengan metode MTT assay. Selanjutnya efek simvastatin terhadap ekspresi cyclin D 1 dan apoptosis dikaji menggunakan flowcytometry menggunakan antibody monoclonal anti-cyclin D 1 dan annexin V-Pi. Hasil penelitian menunjukkan simvastatin mempunyai aktivitas sitotoksik terhadap sel kanker payudara T47D dengan nilai IC 50 sebesar 25,25 ± 1,61 µg/mL. Simvastatin dengan kisaran konsentrasi 6,31 sampai 50,5 µg/mL mampu menurunkan ekspresi cyclin D 1 dengan nilai EC 50 sebesar 18,96 ± 4,42 µg/mL dan menginduksi apoptosis dengan nilai EC 50 sebesar 26,96 ± 6,05 µg/mL. Sebagai kesimpulan, simvastatin menghambat pertumbuhan sel kanker payudara T47D dengan menurunkan ekspresi cyclin D 1 dan menginduksi apoptosis.
Współczesna Onkologia, 2014
Statins (inhibitors of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase) are a group of drugs used to treat lipid disorders. They inhibit cholesterol synthesis at an early stage of the biosynthesis pathway, thus eliminating numerous metabolites involved in the cycle. Numerous studies point to different possible effects of statins on cancer cells. Statins inhibit growth of a tumor, invasion and metastasis formation. They block the production of isoprenoids, which are necessary for post-translational modifications of many proteins, including those involved in normal cell signaling. They also contribute to the reduction in the expression of vascular endothelial growth factor, sensitize tumor cells to NK cell activity, and modify the body inflammatory response. Due to different pharmacokinetic properties of individual statins, they may have opposite effects on the risk of cancer. Currently, most information on the effects of statins on the risk of developing cancer is obtained from observational studies. The studies have different results depending on the location of cancer. The protective effect of statins was observed in the meta-analysis of numerous studies including prostate cancer, stomach cancer, esophagus cancer, and hepatocellular carcinoma; however, it has not yet been confirmed that statins influence the risk of developing colorectal cancer, breast cancer, or lung cancer. The protective effect of statins on the development of many kinds of cancer can be a valuable and easy way to reduce morbidity. However, further research is necessary to thoroughly determine the value of this group of drugs.