Sphingolipid metabolism enzymes as targets for anticancer therapy.

Abstract:

:Treatment with anti-cancer agents in most cases ultimately results in apoptotic cell death of the target tumor cells. Unfortunately, tumor cells can develop multidrug resistance, e.g., by a reduced propensity to engage in apoptosis by which they become insensitive to multiple chemotherapeutics. Ceramide. the central molecule in cellular sphingolipid metabolism, has been recognized as an important mediator of apoptosis. Moreover, an increased cellular capacity for ceramide glycosylation has been identified as a novel multidrug resistance mechanism. Indeed, virtually all multidrug resistant cell types exhibit a deviating sphingolipid composition, most typically an increased level of glucosylceramide. Thus, the enzyme glucosylceramide synthase, which converts ceramide into glucosylceramide, has emerged as a potential target to increase apoptosis and decrease drug resistance of tumor cells. In addition, several other steps in the pathways of sphingolipid metabolism arc altered in multidrug resistant cells, opening a perspective on additional sphingolipid metabolism enzymes as targets for anti-cancer therapy. In this article, we present an overview of the current understanding concerning drug resistance-related changes in sphingolipid metabolism and how interference with this metabolism can be exploited to over come multidrug resistance.

journal_name

Curr Drug Targets

journal_title

Current drug targets

authors

Kok JW,Sietsma H

doi

10.2174/1389450043345452

keywords:

subject

Has Abstract

pub_date

2004-05-01 00:00:00

pages

375-82

issue

4

eissn

1389-4501

issn

1873-5592

journal_volume

5

pub_type

杂志文章,评审
  • Endogenous Cardioprotective Agents: Role in Pre and Postconditioning.

    abstract::Cardiovascular diseases (CVD) are the leading cause of death, chronic illness and disability in Western countries. The most common cause of CVD derives from the harmful effects of acute myocardial ischemia and subsequent reperfusion injury. Cardioprotection against acute ischemia/ reperfusion injury is made possible b...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1389450116666150309115536

    authors: Penna C,Granata R,Tocchetti CG,Gallo MP,Alloatti G,Pagliaro P

    更新日期:2015-01-01 00:00:00

  • Beneficial effects of plant sources on the treatment of osteoporosis.

    abstract::Osteoporosis causes bone loss, and makes bone to susceptible to fracture. The main cause of osteoporosis is estrogen deficiency. Estrogen, calcitonin, calcium, vitamin D and antioxidants can be used to prevent osteoporosis. For the treatment of osteoporosis, the potential biological activities of traditional medicines...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/13894501113149990205

    authors: Süntar I,Akkol EK

    更新日期:2013-12-01 00:00:00

  • Trypanosome RNA polymerases and transcription factors: sensible trypanocidal drug targets?

    abstract::Trypanosomes and Leishmaniae are the agents of several important parasitic diseases threatening hundreds of million human beings worldwide. As they diverged early in evolution, they display original molecular characteristics. These peculiarities are each defining putative specific targets for anti-parasitic drugs. Tra...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/138945008786786064

    authors: Vanhamme L

    更新日期:2008-11-01 00:00:00

  • An Overview of Prospective Drugs for Type 1 and Type 2 Diabetes.

    abstract:AIMS:The aim of this study is to provide an overview of several emerging anti-diabetic molecules. BACKGROUND:Diabetes is a complex metabolic disorder involving the dysregulation of glucose homeostasis at various levels. Insulin, which is produced by β-pancreatic cells, is a chief regulator of glucose metabolism, regul...

    journal_title:Current drug targets

    pub_type: 杂志文章

    doi:10.2174/1389450120666191031104653

    authors: Wu P,Liu Z,Jiang X,Fang H

    更新日期:2020-01-01 00:00:00

  • The link between Hepatic Vitamin A Metabolism and Nonalcoholic Fatty Liver Disease.

    abstract::The liver is essential for the control of glucose and lipid metabolism. Excessive accumulation of fat in the liver disturbs its function and leads to the development of fatty liver diseases. The nonalcoholic fatty liver disease (NAFLD) is a common type of fatty liver disease found in patients who have not consumed sig...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1389450116666150325231015

    authors: Chen G

    更新日期:2015-01-01 00:00:00

  • Biomarkers, critical disease pathways, drug targets, and alternative medicine in male breast cancer.

    abstract::While breast cancer (BC) is commonest malignancy among female with highest death rate, male breast cancer (MBC) is very rare but exhibits highest cancer specific death in men and the incidences of MBCs are rising rapidly. Due to rarity of the disease, no detail information about biomarkers and drug targets available a...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/138945009787122842

    authors: Barh D

    更新日期:2009-01-01 00:00:00

  • Nitrite-stimulated Gastric Formation of S-nitrosothiols As An Antihypertensive Therapeutic Strategy.

    abstract::Hypertension is usually associated with deficient nitric oxide (NO) bioavailability, and therefore stimulating NO activity is an important antihypertensive strategy. Recently, many studies have shown that both nitrite and nitrate anions are not simple products of NO metabolism and indeed may be reduced back to NO. Whi...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1389450119666180816120816

    authors: Oliveira-Paula GH,Tanus-Santos JE

    更新日期:2019-01-01 00:00:00

  • Rationale and Prospects of Targeting Bacterial Two-component Systems for Antibacterial Treatment of Cystic Fibrosis Patients.

    abstract::Bacterial respiratory infections are the main reason of morbidity and mortality among cystic fibrosis (CF) patients. In early childhood, the respiratory infections are due to Staphylococcus aureus and Haemophilus influenzae. In older CF patients, pathogenic Gram-negative bacteria like Achromobacter xylosoxidans, Burkh...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1389450117666160208145934

    authors: Velikova N,Wells JM

    更新日期:2017-01-01 00:00:00

  • Progress of HDAC inhibitor panobinostat in the treatment of cancer.

    abstract::Histone deacetylases are a class of enzymes that play important roles in post translational modifications of histones by deacetylating the lysine residues as well as interacting with various non-histone proteins. This type of enzymes is closely related to oncogenesis and has been proved to be attractive targets for de...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1389450115666140306152642

    authors: Li X,Zhang J,Xie Y,Jiang Y,Yingjie Z,Xu W

    更新日期:2014-06-01 00:00:00

  • Advances in Inhibitors of FXa.

    abstract::Thromboembolic diseases such as deep vein thrombosis (DVT), pulmonary embolism (PE), myocardial infarction (MI) and ischemic strokes are mainly responsible for people's morbidity and mortality and have severely affected the people's quality of life all over the world. According to WHO statistics, an average of 17 mill...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1389450116666150518095533

    authors: Guo L,Ma S

    更新日期:2015-01-01 00:00:00

  • microRNAs: innovative targets for cerebral ischemia and stroke.

    abstract::Stroke is one of the leading causes of death and disability worldwide. Because stroke is a multifactorial disease with a short therapeutic window many clinical stroke trials have failed and the only currently approved therapy is thrombolysis. MicroRNAs (miRNA) are endogenously expressed noncoding short single-stranded...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/138945013804806424

    authors: Ouyang YB,Stary CM,Yang GY,Giffard R

    更新日期:2013-01-01 00:00:00

  • Thrombomodulin links coagulation to inflammation and immunity.

    abstract::Thrombomodulin (TM) is a type 1 membrane bound glycoprotein that has a C-type lectin domain at its Nterminus, 6 copies of the epidermal growth factor-like (EGF) motif and serine/threonine rich domain carrying a glycosoaminoglycan external to the membrane. TM binds thrombin changing thrombin's substrate specificity fro...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/138945012799424606

    authors: Morser J

    更新日期:2012-03-01 00:00:00

  • Targeting JAK3 and BTK tyrosine kinases with rationally-designed inhibitors.

    abstract::Multifunctional rational drug design of protein tyrosine kinases inhibitors allows a potent drug to be utilized to treat more than one disease for greater patient benefits. Many protein tyrosine kinases (PTK), including Janus kinase 3 (JAK3) and Bruton's tyrosine kinase (BTK), have been identified as potential drug ta...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/138945006776054997

    authors: Vassilev AO,Tibbles HE,DuMez D,Venkatachalam TK,Uckun FM

    更新日期:2006-03-01 00:00:00

  • Baculovirus late and very late gene regulation.

    abstract::Baculoviruses have adapted novel tactics to transcribe their genes during the late stages of replication. These include a DNA-directed RNA polymerase which is evolutionarily divergent from cellular polymerases. The viral RNA polymerase is a multisubunit and multifunctional RNA polymerase that has the ability to recogn...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/138945007782151324

    authors: Passarelli AL,Guarino LA

    更新日期:2007-10-01 00:00:00

  • HIV-1 TAT and IMMUNE DYSREGULATION in AIDS PATHOGENESIS: a THERAPEUTIC TARGET.

    abstract::The HIV-1 transactivator Tat protein plays a key role in AIDS pathogenesis. Besides the Tat role as activator of HIV-1 transcription, it exerts several important functions on infected and uninfected cells. In fact, HIV-1 Tat is released by infected cells and is taken up by neighboring cells. In this way it regulates e...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1389450116666150825110658

    authors: Chiozzini C,Toschi E

    更新日期:2016-01-01 00:00:00

  • Three-Dimensional Manufactured Supports for Breast Cancer Stem Cell Population Characterization.

    abstract::Breast Cancer (BC) is the most common cancer among women and the second cause of female death for cancer. When the tumor is not correctly eradicated, there is a high relapse risk and incidence of metastasis. Breast Cancer Stem Cells (BCSCs) are responsible for initiating tumors and are resistant to current anticancer ...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1389450120666181122113300

    authors: Polonio-Alcalá E,Rabionet M,Ruiz-Martínez S,Ciurana J,Puig T

    更新日期:2019-01-01 00:00:00

  • Animal models of carcinogenesis in inflamed colorectum: potential use in chemoprevention study.

    abstract::Inflammation is a risk factor for cancer development in several tissues. In the colorectum, inflammatory bowel disease (ulcerative colitis and Crohn's disease) is a longstanding inflammatory disease with increased risk for colorectal cancer (CRC). Several molecular events involving in chronic inflammatory process cont...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/138945012804545452

    authors: Tanaka T

    更新日期:2012-12-01 00:00:00

  • Aldose reductase, still a compelling target for diabetic neuropathy.

    abstract::Aldose reductase (AR) enzymatically transforms cytosolic glucose into sorbitol, a molecule that poorly penetrates cell membranes and is sometimes slowly metabolized. Hyperglycemia can cause intracellular accumulation of sorbitol and its metabolite, fructose, which can create osmotic swelling and cell dysfunction. Driv...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/138945008783431781

    authors: Oates PJ

    更新日期:2008-01-01 00:00:00

  • PPARs: a potential target for a disease-modifying strategy in stroke.

    abstract::Stroke is one of the major causes of mortality and disability in adults in industrialized countries. Despite numerous preclinical studies and clinical trials in the field of cerebral ischemia, no pharmacological agent has been validated in the treatment of acute ischemic, except thrombolysis. Cerebral ischemia is not ...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1389450111314070005

    authors: Ouk T,Potey C,Gautier S,Bastide M,Deplanque D,Staels B,Duriez P,Leys D,Bordet R

    更新日期:2013-06-01 00:00:00

  • Targeting c-MET/HGF signaling pathway in upper gastrointestinal cancers: rationale and progress.

    abstract::Aberrant activation of receptor-tyrosine kinase c-Met/HGF pathway is shown to be associated with cell proliferation, invasion, metastasis and poor-prognosis in several tumor types, including upper gastrointestinal-malignancies. The interaction of c-Met with multiple signalling-pathways involved in tumorigenic-properti...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1389450115666141107105456

    authors: Gholamin S,Fiuji H,Maftouh M,Mirhafez R,Shandiz FH,Avan A

    更新日期:2014-01-01 00:00:00

  • Non-Small Cell Lung Carcinoma: An Overview on Targeted Therapy.

    abstract::Non-small cell lung cancer (NSCLC) represents close to 90% of all lung cancers. When diagnosed, most cases are on an advanced and inoperable stage, with limited therapeutic options. Existing therapies have shown to be insufficient and novel strategies are urgently necessary. New advances in understanding the disease a...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1389450115666140528151649

    authors: Nascimento AV,Bousbaa H,Ferreira D,Sarmento B

    更新日期:2015-01-01 00:00:00

  • Tachykinins: role in human gastrointestinal tract physiology and pathology.

    abstract::Tachykinins (TKs) and their receptors (NK1, NK2 and NK3), which are diffusely expressed in the human gastrointestinal tract, represent an endogenous modulator system regulating enteric secretomotor functions, inflammatory and immune responses, and visceral hypersensitivity, mainly during pathological gut diseases. Pat...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/138945006778019354

    authors: Improta G,Broccardo M

    更新日期:2006-08-01 00:00:00

  • Zoledronic Acid: Pleiotropic Anti-Tumor Mechanism and Therapeutic Outlook for Osteosarcoma.

    abstract:BACKGROUND:Osteosarcoma is considered the most frequent primary bone malignancy. Lung metastasis is the leading cause of death and the most consistent factor for predicting negative patient outcome in osteosarcoma. Third-generation nitrogen-containing bisphosphonates, such as zoledronic acid, have been shown to reduce ...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1573399811666150615145409

    authors: Ouyang Z,Li H,Zhai Z,Xu J,Dass CR,Qin A,Dai K

    更新日期:2018-01-01 00:00:00

  • Pharmacogenomics in the Americas: the impact of genetic admixture.

    abstract::In this review we focus on the impact of genetic admixture on pharmacogenomics in the American continent, where five centuries of intermarriage between Amerindians, European and Africans, resulted in the extensive population heterogeneity observed nowadays. We compare two alternative views of human genomic variation, ...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/138945006779025392

    authors: Suarez-Kurtz G,Pena SD

    更新日期:2006-12-01 00:00:00

  • Doxorubicin Action on Mitochondria: Relevance to Osteosarcoma Therapy?

    abstract:BACKGROUND:The mitochondria may very well determine the final commitment of the cell to death, particularly in times of energy stress. Cancer chemotherapeutics such as the anthracycline doxorubicin perturb mitochondrial structure and function in tumour cells, as evidenced in osteosarcoma, for which doxorubicin is used ...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1389450116666150416115852

    authors: Armstrong J,Dass CR

    更新日期:2018-01-01 00:00:00

  • Recognition of Plasminogen Activator Inhibitor Type 1 as the Primary Regulator of Fibrinolysis.

    abstract::The fibrinolytic system consists of a balance between rates of plasminogen activation and fibrin degradation, both of which are finely regulated by spatio-temporal mechanisms. Three distinct inhibitors of the fibrinolytic system that differently regulate these two steps are plasminogen activator inhibitor type-1 (PAI-...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1389450120666190715102510

    authors: Urano T,Suzuki Y,Iwaki T,Sano H,Honkura N,Castellino FJ

    更新日期:2019-01-01 00:00:00

  • Insight into Pain Modulation: Nociceptors Sensitization and Therapeutic Targets.

    abstract::Pain is a complex multidimensional concept that facilitates the initiation of the signaling cascade in response to any noxious stimuli. Action potential generation in the peripheral nociceptor terminal and its transmission through various types of nociceptors corresponding to mechanical, chemical or thermal stimuli le...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1389450120666190131114244

    authors: Khan A,Khan S,Kim YS

    更新日期:2019-01-01 00:00:00

  • Gabapentin and pregabalin for the acute post-operative pain management. A systematic-narrative review of the recent clinical evidences.

    abstract:BACKGROUND:Gabapentin and pregabalin inhibit Ca(2+) currents via high-voltage-activated channels containing the alpha2delta-1 subunit, reducing neurotransmitter release and attenuating the postsynaptic excitability. They are antiepileptic drugs successfully used also for the chronic pain treatment. A large number of cl...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/138945009788982513

    authors: Dauri M,Faria S,Gatti A,Celidonio L,Carpenedo R,Sabato AF

    更新日期:2009-08-01 00:00:00

  • Possible Effects of Dietary Anthocyanins on Diabetes and Insulin Resistance.

    abstract::Diabetes is reaching epidemic proportions worldwide. Many dietary compounds have been found to exert health beneficial effects against different pathologies including diabetes. Most bioactive compounds have been identified in fruits and vegetables and their mechanisms of action explored both in vitro and in vivo. In p...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1389450116666151001105230

    authors: Turrini E,Ferruzzi L,Fimognari C

    更新日期:2017-01-01 00:00:00

  • Aging of Brain Related with Mitochondrial Dysfunctions.

    abstract::Advancing age presents a major challenge for the elderly population in terms of quality of life. The risk of cognitive impairment, motor in-coordination, and behavioral inconsistency due to neuronal damage is relatively higher in aging individuals of society. The brain, through its structural and functional integrity,...

    journal_title:Current drug targets

    pub_type: 杂志文章

    doi:10.2174/1389450121999201209202247

    authors: Dhote V,Samundre P,Ganeshpurkar A,Upaganlawar A

    更新日期:2020-12-09 00:00:00