Abstract:
:DNA methyltransferase (DNMT) and histone deacetylase are key enzymes mediating the epigenetic regulation of gene expression. DNA hypermethylation and/or histone deacetylation in promoter regions is often associated with downregulation or silencing of transcription. Epigenetic silencing of tumor suppressor genes plays an important role in malignant transformation. DNMT and HDAC inhibitors induce DNA demethylation and histone acetylation, respectively, leading to reactivation of silenced genes, and dramatic morphological and functional changes in cancer cells. In this study, we have conducted a series of experiments to characterize the effects of epigenetic inhibitors in endometrial cancer cells. Using cell lines representing different stages of endometrioid cancers, we examined the impact of DNMT inhibitor, ADC, and HDAC inhibitor, TSA, on cell cycle and apoptosis. We found that while both reagents were capable of inhibiting cell proliferation and inducing cell apoptosis, TSA appeared to be a more potent apoptosis inducer, but with a smaller effect on cell cycle. On the other hand, ADC exhibited strong effects on cell cycle regulation, but had smaller impact on cell apoptosis. We subsequently confirmed the presence of a strong synergism between DNMT and HDAC inhibitors. Thus, ADC and TSA exhibited strong cytostatic and apoptotic effects in endometrial cancer cell lines and the combined application may deliver the highest response in the clinical setting.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
Xu S,Ren J,Chen HB,Wang Y,Liu Q,Zhang R,Jiang SW,Li Jdoi
10.2174/13816128113199990527subject
Has Abstractpub_date
2014-01-01 00:00:00pages
1881-7issue
11eissn
1381-6128issn
1873-4286pii
54339journal_volume
20pub_type
杂志文章abstract::Cell therapy has been proposed to treat patients with end-stage heart failure. However, it has been suggested that the significant mechanical forces in an often ischaemic, inflamed, biochemically hostile environment may cause poor cell survival and retention. It is hypothesised that tissue engineering techniques could...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990442
更新日期:2014-01-01 00:00:00
abstract::Aquaporins (AQPs) are expressed in physiologically essential tissues and organs in which edema and fluid imbalances are of major concern. Potential roles in brain water homeostasis and edema, angiogenesis, cell migration, development, neuropathological diseases, and cancer suggest that this family of membrane proteins...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161207782341349
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abstract::Alzheimer's disease (AD) is a complex degenerative disorder of the brain, associated with a progressive cognitive decline. Age is the main risk factor with almost half of the population above 90 years affected by this pathology. AD and brain aging share common molecular changes, so it has been hypothesized that AD cou...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:
更新日期:2013-01-01 00:00:00
abstract::Humans have always lived with tubercle bacilli. Host susceptibility both inherited and acquired determines whether an individual infected with Mycobacterium tuberculosis will eventually fall ill and develop tuberculosis (TB). After infection with M. tuberculosis, a latent TB infection may ensue reflected by immune r...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161211797470228
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abstract::In order to develop an effective pharmacological treatment for obesity, an endogenous factor that promotes a positive energy balance by increasing appetite and decreasing fat oxidation could represent the drug target scientists have been looking for. The recently discovered gastric endocrine agent ghrelin, which appea...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612033454748
更新日期:2003-01-01 00:00:00
abstract::Cardiac ischemia, followed by reperfusion, often results in the development of cardiac contractile dysfunction that limits the recovery prognosis of patients. The current goal of pharmacological therapy in the course of ischemic heart disease is to improve the oxygen supply/demand ratio for the heart. Cardiac contract...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990556
更新日期:2014-01-01 00:00:00
abstract::Inflammatory Bowel Diseases (IBD) are now widely receiving attention. There are many reasons why people get IBD; for example, environment, smoking, family heredity, intestinal microbiota and so on. Antibiotics have not been proven effective and those suffering from IBD have begun to look for other effective drugs to t...
journal_title:Current pharmaceutical design
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doi:10.2174/1381612824666180829103945
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abstract::Myelodysplastic syndromes (MDS) are a group of aquired hematopoietic disorders characterized by ineffective hematopoiesis, and increased risk of progression of acute myeloid leukemia. For a long period of time, the standard therapy for MDS was hematopoietic stem cell transplantation, however DNA methyltransferase inhi...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
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更新日期:2012-01-01 00:00:00
abstract::In recent years, combination of different types of therapies using nanoparticles has emerged as an advanced strategy for cancer treatment. Most of all, combination of chemotherapeutic drug and siRNA in nanoformulation has shown a great potential, because siRNA-mediated specific gene silencing can compensate for the in...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150531165059
更新日期:2015-01-01 00:00:00
abstract:BACKGROUND:According to the World Health Organization (WHO), diabetes mellitus is considered the 7th leading cause of death as of 2016, while almost half of all deaths related to high blood glucose occur before the age of 70. According to the 2019 American Diabetes Association's (ADA) guidelines, metformin is the first...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200408095310
更新日期:2020-01-01 00:00:00
abstract::In recent years, the simple paradigm of adipose tissue as merely a fat store is rapidly evolving into a complex paradigm of this tissue as multipotential secretory organ, partitioned into a few large depots, including visceral and subcutaneous location, and many small depots, associated with a variety of organs in the...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
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更新日期:2003-01-01 00:00:00
abstract:BACKGROUND:In the field of forensic toxicology, the quality of analytical methods is of great importance to ensure the reliability of results and to avoid unjustified legal consequences. A key to high quality analytical methods is a thorough method development. METHODS:The presented article will provide an overview on...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666170622113331
更新日期:2017-01-01 00:00:00
abstract::Protein-protein interactions (PPI) are involved in vital cellular processes and are therefore associated to a growing number of diseases. But working with them as therapeutic targets comes with some major hurdles that require substantial mutations from our way to design drugs on historical targets such as enzymes and ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212802651571
更新日期:2012-01-01 00:00:00
abstract:BACKGROUND:Radix Stephaniae Tetrandrine (RST), known as FangJi (Pinyin name) in Chinese, is the dried root of Stephania tetrandra S.Moore, and has been prescribed in combination with other herbs to treat cardiovascular diseases and breast cancer in traditional Chinese medicine (TCM) clinical trials. OBJECTIVE:The aim ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612826666200110143706
更新日期:2020-01-01 00:00:00
abstract::Acute kidney injury (AKI) is relatively common in patients undergoing transcatheter aortic valve implantation (TAVI) and has been associated with increased mortality and worse outcomes. The administration of iodinated contrast media in an elderly population with increased rates of chronic kidney injury and heart failu...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666151208120522
更新日期:2016-01-01 00:00:00
abstract::Cytokines are glycoproteins that serve as chemical messengers between cells. They assist in the regulation of cell growth and repair and also have immune modulating properties. Cytokines play a role in diverse clinical processes and phenomena such as fatigue, fever, sleep, pain, stress and aching. A review of the fibr...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:
更新日期:2006-01-01 00:00:00
abstract:BACKGROUND:Sulfur mustard (SM)-induced airway injuries and chronic obstructive pulmonary disease (COPD) are characterized by chronic inflammation of the respiratory tract and share some similarities regarding the cellular and molecular mechanisms orchestrating airway destruction. Since available data regarding the immu...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160307150818
更新日期:2016-01-01 00:00:00
abstract::MNPs find numerous important biomedical applications owing to their high biocompatibility and unique magnetic properties at the bottom level. Among several other biomedical applications, MNPs are gaining importance in treating various kinds of cancer either as a hyperthermia agent alone or as a drug/gene carrier for s...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1389203720666190521114936
更新日期:2019-01-01 00:00:00
abstract::Stimulant use disorders are an unrelenting public health concern worldwide. Agonist replacement therapy is among the most effective strategies for managing substance use disorders including nicotine and opioid dependence. The present paper reviewed clinical data from human laboratory self-administration studies and cl...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161281940131209142843
更新日期:2013-01-01 00:00:00
abstract::Effective blood pressure control with a large arsenal of conventional antihypertensive drugs, such as diuretics, beta-adrenergic blockers, and calcium channel blockers, significantly reduce the morbidity and mortality associated with cardiovascular disease. However, blood pressure control with these drugs does not red...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
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更新日期:2007-01-01 00:00:00
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journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200909125354
更新日期:2020-09-09 00:00:00
abstract:BACKGROUND:Hepatocellular carcinoma (HCC) has high mortality partly due to acquiring drug resistance during chemotherapy treatment. Therefore, it is necessary to explore the underlying mechanism of drug resistance. METHODS:We used 2-DE and MALDI-TOF-MS analysis to explore the possible molecular insight into 5-FU resis...
journal_title:Current pharmaceutical design
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doi:10.2174/138161282001140113125143
更新日期:2014-01-01 00:00:00
abstract::Development of effective drug delivery systems is important for medicine and healthcare. Polymer particulates (micro- and nanoparticles) have opened new opportunities in the field of drug delivery by overcoming various limitations of conventional delivery methods. The properties of polymeric particles can be readily t...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160217125734
更新日期:2016-01-01 00:00:00
abstract::The activation of Corticotrophin Releasing-Factor (CRF) receptors in the brain is well established to coordinate the endocrine, behavioral, autonomic and visceral responses to stress. In addition, CRF receptors are also expressed within the gut where they exert biological actions and play a role in modulating stress-r...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666170228142428
更新日期:2017-01-01 00:00:00
abstract::The concept of probiotics has evolved immensely since it was first proposed a century ago. There are numerous potential health benefits attributed to certain probiotic bacteria, from preventing gastrointestinal (GI) infections to stimulating the immune system. Recent evidence is now quite compelling for a role of prob...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208784480234
更新日期:2008-01-01 00:00:00
abstract::Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent causes of hepatic dysfunction and is highly correlated with components of the metabolic syndrome such as obesity, insulin resistance and type 2 diabetes. Among others, nutritional factors, physical inactivity, genetic variants and visceral obesity h...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161210791208938
更新日期:2010-06-01 00:00:00
abstract::Aspirin is the cornerstone of treatment in patients with coronary artery disease. However, several studies investigating the in vitro response of platelets to the administration of aspirin showed this response to be variable, with some patients exhibiting non-responsiveness or resistance. Aspirin resistance may be cat...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
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更新日期:2009-01-01 00:00:00
abstract:BACKGROUND:Inhibition of hepatic fibrosis is an attainable objective in managing the chronic liver disease. The present study aimed to investigate possible defensive effects of metformin on the activities of antioxidant enzymes, hydroxyproline content, and biochemical factors in bile duct ligation (BDL)-induced cholest...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612824666181003114108
更新日期:2018-01-01 00:00:00
abstract::Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming the most common cause of chronic liver disease worldwide. This is primarily driven by the global epidemic of obesity and diabetes as well as the aging of the general population. Most of the epidemiology data of NAFLD for North America are published from stud...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612826666200303114934
更新日期:2020-01-01 00:00:00
abstract::There is an increasing need to rapidly determine the specificity of proteases that potentially play a role in human and animal disease. Substrates for novel proteases can be discovered by testing standard protease substrates such as oxidized insulin B-chain, by screening commercially available substrates for other pro...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612023392630
更新日期:2002-01-01 00:00:00