973 results match your criteria simvastatin cancer

A Chemokine Regulatory Loop Induces Cholesterol Synthesis in Lung-Colonizing Triple-Negative Breast Cancer Cells to Fuel Metastatic Growth.

Mol Ther 2021 Jul 15. Epub 2021 Jul 15.

Department of Surgery, Samuel Oschin Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. Electronic address:

Triple-negative breast cancer (TNBC) has a high propensity for organ-specific metastasis. However, the underlying mechanisms are not well understood. Here, we show that the primary TNBC tumor-derived C-X-C motif chemokines 1/2/8 (CXCL1/2/8) stimulate lung resident fibroblasts to produce C-C motif chemokines 2/7 (CCL2/7), which in turn activate cholesterol synthesis in lung-colonizing TNBC cells and induce angiogenesis at lung metastatic sites. Read More

View Article and Full-Text PDF

Comparison of Transcriptomic Profiles of MiaPaCa-2 Pancreatic Cancer Cells Treated with Different Statins.

Molecules 2021 Jun 9;26(12). Epub 2021 Jun 9.

Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University, Špitálska 24, 813 72 Bratislava, Slovakia.

Statins have been widely used for the treatment of hypercholesterolemia due to their ability to inhibit HMG-CoA reductase, the rate-limiting enzyme of de novo cholesterol synthesis, via the so-called mevalonate pathway. However, their inhibitory action also causes depletion of downstream intermediates of the pathway, resulting in the pleiotropic effects of statins, including the beneficial impact in the treatment of cancer. In our study, we compared the effect of all eight existing statins on the expression of genes, the products of which are implicated in cancer inhibition and suggested the molecular mechanisms of their action in epigenetic and posttranslational regulation, and in cell-cycle arrest, death, migration, or invasion of the cancer cells. Read More

View Article and Full-Text PDF

Effects of Alcoholic Extracts of Bangladeshi Mangrove Linn. (Acanthaceae) Leaf and Stem on Atherogenic Model of Wistar Albino Rats.

Evid Based Complement Alternat Med 2021 30;2021:7539037. Epub 2021 May 30.

Department of Biochemistry and Molecular Biology, Trust University, Barishal, Ruiya, Nobogram Road, Barishal 8200, Bangladesh.

Linn. (Acanthaceae) is a popular mangrove ethnomedicinal plant that cures several ailments, including asthma, diabetes, cancer, and many others. Our experiment was aimed at evaluating the anti-atherogenic effect of (leaf and stem) on a high-fat diet-induced atherogenic rat model. Read More

View Article and Full-Text PDF

Comparative hepatic and intestinal efflux transport of statins.

Drug Metab Dispos 2021 Jun 23. Epub 2021 Jun 23.

Department of Clinical Pharmacology, University of Helsinki, Finland

Previous studies have shown that lipid-lowering statins are transported by various ATP-binding cassette (ABC) transporters. However, due to varying methods, it is difficult to compare the transport profiles of statins. Therefore, we investigated the transport of ten statins or statin metabolites by six ABC transporters using human embryonic kidney cell-derived membrane vesicles. Read More

View Article and Full-Text PDF

Lactate dehydrogenase B regulates macrophage metabolism in the tumor microenvironment.

Theranostics 2021 4;11(15):7570-7588. Epub 2021 Jun 4.

Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, 60590 Frankfurt, Germany.

: Glucose metabolism in the tumor-microenvironment is a fundamental hallmark for tumor growth and intervention therein remains an attractive option for anti-tumor therapy. Whether tumor-derived factors such as microRNAs (miRs) regulate glucose metabolism in stromal cells, especially in tumor-associated macrophages (TAMs), to hijack them for trophic support, remains elusive. : Ago-RIP-Seq identified macrophage lactate dehydrogenase B (LDHB) as a target of tumor-derived miR-375 in both 2D/3D cocultures and in murine TAMs from a xenograft mouse model. Read More

View Article and Full-Text PDF

Simvastatin-romidepsin combination kills bladder cancer cells synergistically.

Transl Oncol 2021 Sep 16;14(9):101154. Epub 2021 Jun 16.

Department of Urology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan. Electronic address:

The HMG-CoA reductase inhibitor simvastatin activates AMP-activated protein kinase (AMPK) and thereby induces histone acetylation. We postulated that combining simvastatin with the histone deacetylase (HDAC) inhibitor romidepsin would kill bladder cancer cells by inducing histone acetylation cooperatively. The combination of romidepsin and simvastatin induced robust apoptosis and killed bladder cancer cells synergistically. Read More

View Article and Full-Text PDF
September 2021

Importance of Mevalonate Pathway Lipids on the Growth and Survival of Primary and Metastatic Gastric Carcinoma Cells.

Clin Exp Gastroenterol 2021 31;14:217-228. Epub 2021 May 31.

Departamento de Bioquímica, Escuela de Medicina, Universidad de Costa Rica, San José, Costa Rica.

Purpose: This preclinical study aims to determine the effect of drugs that alter isoprenoids and cholesterol metabolism in the homeostasis of gastric carcinoma cell lines in the search for new therapeutic targets for stomach cancer.

Materials And Methods: Primary (AGS) and metastatic (NCI-N87) gastric cancer cell lines were treated with simvastatin and terbinafine, two inhibitors of the mevalonate pathway, and avasimibe, an inhibitor of cholesterol esterification. Cell viability and growth were measured as well as cholesterol levels and the expression of the hydroxy methyl-glutaryl CoA reductase (HMGCR) and the LDL receptor (LDLR). Read More

View Article and Full-Text PDF

Association Between Iron and Cholesterol in Neuroblastomas.

Anticancer Res 2021 Jun;41(6):2795-2804

Department of Neurosurgery, Pennsylvania State University College of Medicine, Hershey, PA, U.S.A.

Background/aim: Neuroblastoma is the most common childhood extracranial solid malignancy. Although cancer cells need iron and lipids for active cell division, possible links between iron and lipid metabolism in neuroblastomas have not been studied.

Materials And Methods: We evaluated the levels and association between iron and cholesterol on in vitro neuroblastoma cancer models. Read More

View Article and Full-Text PDF

Assessing the Interactions of Statins with Human Adenylate Kinase Isoenzyme 1: Fluorescence and Enzyme Kinetic Studies.

Int J Mol Sci 2021 May 24;22(11). Epub 2021 May 24.

Faculty of Chemistry, Nicolaus Copernicus University in Toruń, Gagarina 7, 87-100 Toruń, Poland.

Statins are the most effective cholesterol-lowering drugs. They also exert many pleiotropic effects, including anti-cancer and cardio- and neuro-protective. Numerous nano-sized drug delivery systems were developed to enhance the therapeutic potential of statins. Read More

View Article and Full-Text PDF

Reactive oxygen species scavenging and inflammation mitigation enabled by biomimetic prussian blue analogues boycott atherosclerosis.

J Nanobiotechnology 2021 May 31;19(1):161. Epub 2021 May 31.

Department of Medical Ultrasound and Central Laboratory, Shanghai Tenth People's Hospital, Ultrasound Research and Education Institute, Clinical Research Center for Interventional Medicine, Tongji University School of Medicine, Shanghai Engineering Research Center of Ultrasound Diagnosis and Treatment, National Clinical Research Center for Interventional Medicine, No. 301 Yan-chang-zhong Road, Shanghai, 200072, People's Republic of China.

Background: As one typical cardiovascular disease, atherosclerosis severely endanger people' life and cause burden to people health and mentality. It has been extensively accepted that oxidative stress and inflammation closely correlate with the evolution of atherosclerotic plaques, and they directly participate in all stages of atherosclerosis. Regarding this, anti-oxidation or anti-inflammation drugs were developed to enable anti-oxidative therapy and anti-inflammation therapy against atherosclerosis. Read More

View Article and Full-Text PDF

Organ-specific cholesterol metabolic aberration fuels liver metastasis of colorectal cancer.

Theranostics 2021 27;11(13):6560-6572. Epub 2021 Apr 27.

Department of General Surgery, Huashan Hospital & Cancer Metastasis Institute & Institutes of Biomedical Sciences, Fudan University, Shanghai, 200040, China.

Metastasis, the development of secondary malignant growth at a distance from a primary tumor, is the main cause of cancer-associated death. However, little is known about how metastatic cancer cells adapt to and colonize in the new organ environment. Here we sought to investigate the functional mechanism of cholesterol metabolic aberration in colorectal carcinoma (CRC) liver metastasis. Read More

View Article and Full-Text PDF

Targeting Cholesterol Biosynthesis Promotes Anti-tumor Immunity by Inhibiting Long Noncoding RNA SNHG29 Mediated YAP Activation.

Mol Ther 2021 May 13. Epub 2021 May 13.

Department of Pathology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China;; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China;. Electronic address:

Although anti-tumor immunity through checkpoint inhibitors, specifically anti PD-1/PD-L1 interaction, is a promising approach for cancer therapy. However, early clinical trials indicate that colorectal cancer (CRC) do not respond well to immune checkpoint therapies, new effective immunotherapy approaches to CRC warrant further study. Simvastatin is an inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the rate-limiting enzyme of the mevalonate (MVA) pathway for the cholesterol biosynthesis. Read More

View Article and Full-Text PDF

Simvastatin is effective in killing the radioresistant breast carcinoma cells.

Radiol Oncol 2021 May 4. Epub 2021 May 4.

Medical University of Innsbruck, Therapeutic Radiology and Oncology, Innsbruck, Austria.

Background: Statins, small molecular 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, are widely used to lower cholesterol levels in lipid-metabolism disorders. Recent preclinical and clinical studies have shown that statins exert beneficial effects in the management of breast cancer by increasing recurrence free survival. Unfortunately, the underlying mechanisms remain elusive. Read More

View Article and Full-Text PDF

MYBL2 disrupts the Hippo-YAP pathway and confers castration resistance and metastatic potential in prostate cancer.

Theranostics 2021 31;11(12):5794-5812. Epub 2021 Mar 31.

Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, China.

Resistance to androgen-deprivation therapy (ADT) associated with metastatic progression remains a challenging clinical task in prostate cancer (PCa) treatment. Current targeted therapies for castration-resistant prostate cancer (CRPC) are not durable. The exact molecular mechanisms mediating resistance to castration therapy that lead to CRPC progression remain obscure. Read More

View Article and Full-Text PDF

Mini review: The FDA-approved prescription drugs that target the MAPK signaling pathway in women with breast cancer.

Breast Dis 2021 ;40(2):51-62

Fertility, Infertility and Perinatology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Breast cancer (BC) is the most common cancer and the prevalent type of malignancy among women. Multiple risk factors, including genetic changes, biological age, dense breast tissue, and obesity are associated with BC. The mitogen-activated protein kinases (MAPK) signaling pathway has a pivotal role in regulating biological functions such as cell proliferation, differentiation, apoptosis, and survival. Read More

View Article and Full-Text PDF
January 2021

Simvastatin accelerated motoneurons death in SOD1 mice through inhibiting Rab7-mediated maturation of late autophagic vacuoles.

Cell Death Dis 2021 04 12;12(4):392. Epub 2021 Apr 12.

Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, P.R. China.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease caused by motoneuron loss, for which there is currently no effective treatment. Statins, as inhibitors of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, are used as drugs for treatment for a variety of disease such as ischemic diseases, neurodegenerative diseases, cancer, and inflammation. However, our previous evidence has demonstrated that simvastatin leads to cytotoxicity in NSC34-hSOD1 cells by aggravating the impairment of autophagic flux, but the role of simvastatin in ALS model remains elusive. Read More

View Article and Full-Text PDF

Evaluation of Antitumor Efficacy of Chitosan-Tamarind Gum Polysaccharide Polyelectrolyte Complex Stabilized Nanoparticles of Simvastatin.

Int J Nanomedicine 2021 29;16:2533-2553. Epub 2021 Mar 29.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, AIMST University, Kedah, 08100, Malaysia.

Purpose: The present study was intended to fabricate chitosan (Ch)-tamarind gum polysaccharide (TGP) polyelectrolyte complex stabilized cubic nanoparticles of simvastatin and evaluate their potential against human breast cancer cell lines.

Materials And Methods: The antisolvent precipitation method was used for formulation of nanoparticles. Factorial design (3) was utilized as a tool to analyze the effect of Ch and TGP concentration on particle size and entrapment efficiency of nanoparticles. Read More

View Article and Full-Text PDF

LDLR inhibition promotes hepatocellular carcinoma proliferation and metastasis by elevating intracellular cholesterol synthesis through the MEK/ERK signaling pathway.

Mol Metab 2021 Apr 3;51:101230. Epub 2021 Apr 3.

Department of Tumor Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China; National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China. Electronic address:

Objective: Adaptive rewiring of cancer energy metabolism has received increasing attention. By binding with LDLs, LDLRs make most of the circulating cholesterol available for cells to utilize. However, it remains unclear how LDLR works in HCC development by affecting cholesterol metabolism. Read More

View Article and Full-Text PDF

Simvastatin mitigates depressive-like behavior in ovariectomized rats: Possible role of NLRP3 inflammasome and estrogen receptors' modulation.

Int Immunopharmacol 2021 Jun 25;95:107582. Epub 2021 Mar 25.

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt. Electronic address:

It is well known that females are more vulnerable than males to stress-related psychiatric disorders, particularly during perimenopausal and postmenopausal periods. Hormone replacement therapy (HRT) has been widely used for the management of postmenopausal depression. However, HRT could be associated with severe adverse effects, including increased risk for coronary heart disease, breast cancer and endometrial cancer. Read More

View Article and Full-Text PDF

Statins are associated with increased risk of squamous cell carcinoma of the skin: a whole-population study from Iceland.

Arch Dermatol Res 2021 Mar 27. Epub 2021 Mar 27.

Faculty of Medicine, University of Iceland, Saemundargata 2, 101, Reykjavík, Iceland.

Statins have been associated with an increased risk of keratinocyte carcinoma but data are limited and conflicting. Statins are hypothesized to contribute to KC through immunomodulation. A whole-population case-control study of the Icelandic population was conducted using the Icelandic Cancer Registry and Icelandic Prescription Medicine Register. Read More

View Article and Full-Text PDF

Simvastatin inhibits oral squamous cell carcinoma by targeting TMEM16A Ca-activated chloride channel.

J Cancer Res Clin Oncol 2021 Jun 23;147(6):1699-1711. Epub 2021 Mar 23.

Liaoning Provincial Key Laboratory of Oral Diseases, Department of Oromaxillofacial-Head and Neck Surgery, School and Hospital of Stomatology, China Medical University, 117 Nanjing Bei Jie, Heping District, Shenyang,, 110002, Liaoning, China.

Purpose: Ca-activated chloride channel TMEM16A has been found to be overexpressed in many cancers including head and neck squamous cell carcinoma (HNSCC). Nevertheless, the role of TMEM16A in oral squamous cell carcinoma (OSCC) remains unclear. Although simvastatin is known to produce anti-tumor effect, the mechanisms by which simvastatin inhibits cancer remain unclear. Read More

View Article and Full-Text PDF

REP1 deficiency causes systemic dysfunction of lipid metabolism and oxidative stress in choroideremia.

JCI Insight 2021 May 10;6(9). Epub 2021 May 10.

Department of Development, Ageing and Disease, UCL Institute of Ophthalmology, London, United Kingdom.

Choroideremia (CHM) is an X-linked recessive chorioretinal dystrophy caused by mutations in CHM, encoding for Rab escort protein 1 (REP1). Loss of functional REP1 leads to the accumulation of unprenylated Rab proteins and defective intracellular protein trafficking, the putative cause for photoreceptor, retinal pigment epithelium (RPE), and choroidal degeneration. CHM is ubiquitously expressed, but adequate prenylation is considered to be achieved, outside the retina, through the isoform REP2. Read More

View Article and Full-Text PDF

Kinome-wide analysis of the effect of statins in colorectal cancer.

Br J Cancer 2021 Jun 19;124(12):1978-1987. Epub 2021 Mar 19.

Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands.

Background: Epidemiological studies and meta-analyses show an association between statin use and a reduced incidence of colorectal cancer (CRC). We have shown that statins act on CRC through bone morphogenetic protein (BMP) signalling, but the exact cellular targets and underlying mechanism of statin action remain elusive. In this study, we set out to assess the influence of statins on global cancer cell signalling by performing an array-based kinase assay using immobilised kinase substrates spanning the entire human kinome. Read More

View Article and Full-Text PDF

MicroRNA-564 inhibits the progression of non-small cell lung cancer via targeting plexin A4.

Exp Ther Med 2021 Apr 13;21(4):358. Epub 2021 Feb 13.

Department of Thoracic Surgery, Huai'an First People's Hospital, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China.

Νon-small cell lung cancer (NSCLC) is the most frequently diagnosed type of cancer, and the most prevalent cause of cancer-associated mortality. The present study aimed to investigate whether microRNA (miR)-564 influences NSCLC progression by regulating NSCLC cell growth and migration, via targeting plexin A4. Therefore, the expression levels of miR-564 and plexin A4 were evaluated in NSCLC specimens or cells using reverse transcription-quantitative PCR. Read More

View Article and Full-Text PDF

Combination of Simvastatin and FAC Improves Response to Neoadjuvant Chemotherapy in Advanced Local Breast Cancer.

Cancer Res Treat 2021 Mar 9. Epub 2021 Mar 9.

Department of Surgical Oncology, Koja General Hospital, Jakarta, Indonesia.

Purpose: The efficacy of neoadjuvant chemotherapy (NAC) for Locally Advanced Breast Cancer (LABC) is limited due to drug resistance and cardiotoxic effects. Pre-clinical studies have shown that statin induces apoptosis and decreases breast cancer cell growth. This study aims to evaluate the role of statin in combination with Fluorouracil, Adriamycin, and Cyclophosphamide (FAC) therapy in LABC patients. Read More

View Article and Full-Text PDF

Comparison of the Effects of Statins on A549 Nonsmall-Cell Lung Cancer Cell Line Lipids Using Fourier Transform Infrared Spectroscopy: Rosuvastatin Stands Out.

Lipids 2021 05 21;56(3):289-299. Epub 2021 Feb 21.

Department of Food Engineering, Faculty of Engineering, İzmir Institute of Technology, Urla, 35430, İzmir, Turkey.

Statins are commonly prescribed antilipidemic and anticholesterol class of drugs. In addition to their major role, they have been found to have anticancer effects on in vitro, animal and clinical studies. The aim of this study was to investigate the effects of six different statins (rosuvastatin, pravastatin, simvastatin, lovastatin, fluvastatin, and atorvastatin) on A549 cancer cells lipids by Fourier transform infrared (FTIR) spectroscopy. Read More

View Article and Full-Text PDF

Simvastatin enhances the efficacy of nilotinib in chronic myeloid leukaemia by post-translational modification and drug transporter modulation.

Anticancer Drugs 2021 06;32(5):526-536

Department of Haematology, Singapore General Hospital.

The resistance of chronic myeloid leukaemia (CML) to tyrosine kinase inhibitors (TKIs) remains a significant clinical problem. Targeting alternative pathways, such as protein prenylation, is known to be effective in overcoming resistance. Simvastatin inhibits 3-hydroxy-3-methylglutaryl-CoA reductase (a key enzyme in isoprenoid-regulation), thereby inhibiting prenylation. Read More

View Article and Full-Text PDF

Cytotoxicity of Simvastatin in Human Breast Cancer MCF-7 and MDA-MB-231 Cell Lines.

Asian Pac J Cancer Prev 2021 Feb 1;22(S1):33-42. Epub 2021 Feb 1.

Department of Internal Medicine, Faculty of Medicine Universitas Padjadjaran/Hasan Sadikin General Hospital, Bandung, Indonesia.

Objective: Statins, 3-hydroxy-3-methylglutaryl co-enzyme A (HMG-CoA) reductase inhibitors, have been shown to be effective in the treatment of cardiovascular disease. Recent reports demonstrate an anticancer effect induced by statins on lung and prostate cancer cells. The present study aimed to investigate the therapeutic potential of Simvastatin can serve as chemotherapeutic agent against human breast cancer MCF-7 and MDA-MB-231 cell lines. Read More

View Article and Full-Text PDF
February 2021

Use of Simvastatin, Fibrin Clots, and Their Combination to Improve Human Ovarian Tissue Grafting for Fertility Restoration After Anti-Cancer Therapy.

Front Oncol 2020 22;10:598026. Epub 2021 Jan 22.

Infertility and IVF Unit, Beilinson Women Hospital, Rabin Medical Center, Petach Tikvah, Israel.

Anticancer treatments, particularly chemotherapy, induce ovarian damage and loss of ovarian follicles. There are limited options for fertility restoration, one of which is pre-chemotherapy cryopreservation of ovarian tissue. Transplantation of frozen-thawed human ovarian tissue from cancer survivors has resulted in live-births. Read More

View Article and Full-Text PDF
January 2021

Statins as inhibitors of voltage-gated potassium channels Kv1.3 in cancer cells.

J Mol Struct 2021 Apr 7;1230:129905. Epub 2021 Jan 7.

Department of Biophysics and Neurobiology, Wrocław Medical University, ul. Chałubińskiego 3A, 50-368 Wrocław, Poland.

Voltage-gated potassium channels are integral membrane proteins selectively permeable for potassium ions and activated upon change of membrane potential. Voltage-gated potassium channels of the Kv1.3 type were discovered both in plasma membrane and in inner mitochondrial membrane (mito Kv1. Read More

View Article and Full-Text PDF