All hydrophobic HMG-CoA reductase inhibitors induce apoptotic death in rat pulmonary vein endothelial cells

Kaneta, Shigeru; Satoh, Kumi; Kano, Seiichiro; Kanda, Makoto; Ichihara, Kazuo

doi:10.1016/s0021-9150(03)00301-0

Cited by 100 publications

(71 citation statements)

References 27 publications

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“…Although lovastatin was able to induce apoptosis in these cells, a higher concentra tion (30-50 JM) and a prolonged incubation time (72-96 h) were required to achieve the similar level of apoptosis (data not shown). These results are consistent with the pre vious reports that lovastatin at a higher concentration is needed to induce apoptosis in myeloma plasma cells, smooth muscle cells and endothelial cells [36][37][38], suggest- ing that ovarian cancer cells may be particularly vulnerable to statin-induced apoptosis.…”

Section: Statins Induce Apoptosis In Ovarian Cancer Cellssupporting

confidence: 91%

Statins induce apoptosis in ovarian cancer cells through activation of JNK and enhancement of Bim expression

Liu

Liang

Kumar

et al. 2008

Cancer Chemother Pharmacol

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Purpose Ovarian cancer is the leading cause of death among all gynecological malignancies in Western coun tries. Although therapy for ovarian cancer has been greatly improved in the past 20 years, the overall survival for patients with advanced ovarian cancer has not changed sig niWcantly. The poor survival rates in patients with advanced ovarian cancer are due both to late diagnosis and to lack of eVective drugs for the majority of patients who have a relapse and develop resistance to current chemotherapy agents used for ovarian cancer. Thus, developing and dis covering eVective novel drugs with diVerent molecular structures from conventional chemotherapy agents have become an urgent clinical need.

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Section: Statins Induce Apoptosis In Ovarian Cancer Cellssupporting

confidence: 91%

Statins induce apoptosis in ovarian cancer cells through activation of JNK and enhancement of Bim expression

Liu

Liang

Kumar

et al. 2008

Cancer Chemother Pharmacol

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“…Before we carried out the experiment in vivo using dogs, we confirmed the characteristics of the statins in vitro. Lipophilic statins induce apoptotic cell death in rat pulmonary vein endothelial cells (PVEC), whereas hydrophilic pravastatin does not (15). Because loss of viability of rat PVEC induced by lipophilic statins is abolished by addition of mevalonic acid, these statins enter the cells and inhibit the HMG-CoA reductase inside the cell.…”

Section: Discussionmentioning

confidence: 99%

Effects of Rosuvastatin and Pitavastatin on Ischemia-Induced Myocardial Stunning in Dogs

et al. 2008

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Abstract. Incomplete recovery of myocardial contraction after reperfusion following brief ischemia is called the "stunning phenomenon" in an animal experiment. A hydrophilic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (statin) does not affect this phenomenon, but lipophilic statins further reduce the contraction during reperfusion. The effects of novel hydrophilic rosuvastatin and lipophilic pitavastatin on myocardial stunning in dogs were examined. In a preliminary experiment in vitro, pitavastatin reduced L6 cell viability at 10 −6 M and higher, whereas rosuvastatin and pravastatin up to 10 −5 M did not show such effects. An empty capsule or a capsule filled with rosuvastatin (2 mg / kg per day) or pitavastatin (0.4 mg / kg per day) was orally administered to dogs. After 3 weeks, both statins lowered the serum cholesterol level to the same extent. Under pentobarbital anesthesia, dogs were subjected to 15-min ischemia followed by 120-min reperfusion. Ischemia arrested the myocardial contraction in the ischemic area, and reperfusion recovered it but incompletely, showing the stunning phenomenon. Rosuvastatin did not modify the stunning phenomenon, while pitavastatin further deteriorated the myocardial contraction during reperfusion.

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“…Treatment of proliferating murine tubular cells [50], cultured rat pulmonary vein endothelial cells [51] and the L6 rat skeletal muscle cell line [52] with simvastatin is associated with cell death. In cultured astrocytes from newborn rats, simvastatin causes a time-and dosedependent stellation, followed by apoptosis.…”

Section: Animal Cellsmentioning

confidence: 99%

“…Simvastatin application to human hepatocellular carcinoma HepG2 cells [46], cultured rat pulmonary vein endothelial cells [51] and the L6 rat skeletal muscle cell line [52] is associated with increased DNA oxidative damage and fragmentation. Causal connection between simvastatin effect and nuclear DNA damage is traceable.…”

Section: Mechanisms Of Cytotoxicity Of Simvastatinmentioning

confidence: 99%

“…Human skeletal muscle cells Apoptosis [39] Human T, B and myeloma tumor cells Apoptosis [41] Human leukemia cells HL-60 Apoptosis [49] Human hepatoma cells HepG2 Cell death and DNA oxidative damage [46] PC3 human prostate cancer cell line Apoptosis or necrosis [45] Freshly isolated human pericytes, TR-PCT1 pericyte cell line Apoptosis [42] Myoblasts from human striated muscle Inhibition of proliferation and DNA synthesis [48] Mouse cardiac myocytes Decreased responsiveness to electrical field stimulation [58] Murine tubular cells Apoptosis [50] L6 rat skeletal muscle cell line Cells death and DNA fragmentation [52] Cultured rat astrocytes, cultured rat cerebellar granule neurons Stellation and apoptosis [53] Cultured rat pulmonary vein endothelial cells Reduced cell viability, DNA fragmentation and apoptotic cell death [51] HT144, M14 and SK-MEL-28 melanoma cell lines Apoptosis and inhibition of the cell growth, migration and invasion Table 2. Cytotoxicity of simvastatin.…”

Section: Object Effects Of Simvastatin Refsmentioning

confidence: 99%

See 1 more Smart Citation

Molecular mechanisms of toxicity of simvastatin, widely used cholesterol-lowering drug. A review

Kaminsky

Kosenko

2010

Open Medicine

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AbstractStatins are widely used and well tolerated cholesterol-lowering drugs, and when used for therapy purposes reduce morbidity and mortality from coronary heart disease. Simvastatin is one of nine known statins, specific inhibitors of hepatic enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase, the rate-limiting step of cholesterol biosynthesis, and is believed to reduce plasma cholesterol levels by decreasing the activity of this enzyme. Statin drugs represent the major improvement in the treatment of hypercholesterolemia that constitutes the main origin of atherosclerosis, leading to coronary heart disease. Although statins are generally safe, minor and severe adverse reactions are well known complications of statin use. Adverse events associated with simvastatin therapy are uncommon, but potentially serious. In this review some details about statins including their adverse effects in humans and animals, the effects of simvastatin on various intracellular and mitochondrial processes, and molecular mechanisms underlying simvastatin cytotoxicity are discussed.

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All hydrophobic HMG-CoA reductase inhibitors induce apoptotic death in rat pulmonary vein endothelial cells

Cited by 100 publications

References 27 publications

Statins induce apoptosis in ovarian cancer cells through activation of JNK and enhancement of Bim expression

Statins induce apoptosis in ovarian cancer cells through activation of JNK and enhancement of Bim expression

Effects of Rosuvastatin and Pitavastatin on Ischemia-Induced Myocardial Stunning in Dogs

Molecular mechanisms of toxicity of simvastatin, widely used cholesterol-lowering drug. A review

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