Peptidyl prolyl isomerase, Pin1 is a potential target for enhancing the therapeutic efficacy of etoposide.

Abstract:

:The peptidyl prolyl isomerase (Pin1) that induces cis-trans isomerization of the peptide bond involving serine/threonine-proline has recently been shown to regulate the activity of many phosphoproteins including the ones involved in damage response pathways. We investigated Pin1 as a potential target for enhancing the efficacy of anticancer therapy by studying the effects of juglone, a Pin1 inhibitor on the cytotoxicity of etoposide (a widely used anticancer drug that targets topoisomerase IIα) in human tumor cell lines. Treatment of cells with juglone synergistically enhanced the cytotoxicity of etoposide (loss of clonogenicity) with a tenfold increase when etoposide treatment preceded juglone exposure. On the other hand, the toxicity was than additive when the treatment protocol was reversed (i.e exposure to juglone followed by etoposide treatment). This suggests that Pin1 inhibition possibly reduces the induction of initial DNA damage by etoposide, which was supported by a decrease in the levels of chromatin bound topoIIα. Increase in the etoposide induced toxicity by juglone appeared to be mainly due to enhanced mitotic cell death linked to cytogenetic damage, although a moderate increase in interphase (apoptotic) death was also evident as revealed by DNA degradation (hypodiploid population and TUNEL assay). Since the level of Pin1 is found to be higher in cancer cells, this enzyme could be a potential target for developing an adjuvant to enhance the efficacy of anticancer therapies.

authors

Mathur R,Chandna S,N Kapoor P,S Dwarakanath B

doi

10.2174/156800911794519761

subject

Has Abstract

pub_date

2011-03-01 00:00:00

pages

380-92

issue

3

eissn

1568-0096

issn

1873-5576

pii

EPub-Abstract-CCDT-114

journal_volume

11

pub_type

杂志文章
  • Heat shock protein 90 - a potential target in the treatment of human acute myelogenous leukemia.

    abstract::Heat shock proteins (HSPs) are molecular chaperones that stabilize folding and conformation of normal as well as oncogenic proteins. These chaperones thereby prevent the formation of protein aggregates. HSPs are often overexpressed in human malignancies, including AML. HSP90 is the main chaperon required for the stabi...

    journal_title:Current cancer drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/156800909789271486

    authors: Reikvam H,Ersvaer E,Bruserud O

    更新日期:2009-09-01 00:00:00

  • Targeting NUPR1 for Cancer Treatment: A Risky Endeavor.

    abstract::NUPR1 is a transcription factor that has attracted great attention because of its various roles in cancer. Several studies were carried out to determine its molecular targets and mechanism of action to develop novel therapies against cancer. Here, we shed light on the role of NUPR1 in different types of cancer. NUPR1 ...

    journal_title:Current cancer drug targets

    pub_type: 杂志文章

    doi:10.2174/1568009620666200703152523

    authors: Mansour SMA,Ali SA,Nofal S,Soror SH

    更新日期:2020-01-01 00:00:00

  • Modification of alternative splicing by antisense oligonucleotides as a potential chemotherapy for cancer and other diseases.

    abstract::It has been estimated that greater than 35% of all human genes undergo alternative splicing. The process of alternative splicing is highly regulated and disruption of a splicing pattern can produce splice variants that have different functions. Certain splice variants that are associated with induction of cell death, ...

    journal_title:Current cancer drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1568009013334124

    authors: Mercatante DR,Sazani P,Kole R

    更新日期:2001-11-01 00:00:00

  • The urokinase plasminogen activator system: a target for anti-cancer therapy.

    abstract::The urokinase plasminogen activator (uPA) system (uPAS) consists of the uPA, its cognate receptor (uPAR) and two specific inhibitors, the plasminogen activator inhibitor 1 (PAI-1) and 2 (PAI-2). The uPA converts the proenzyme plasminogen in the serine protease plasmin, involved in a number of physiopathological proces...

    journal_title:Current cancer drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/156800909787314002

    authors: Ulisse S,Baldini E,Sorrenti S,D'Armiento M

    更新日期:2009-02-01 00:00:00

  • Emerging role of endoglin (CD105) as a marker of angiogenesis with clinical potential in human malignancies.

    abstract::Angiogenesis is crucial for tumor development and progression, and antiangiogenetic therapy represents a promising approach for cancer treatment. Thus, the in-depth understanding of the molecular mechanism(s) regulating angiogenesis, together with the characterization of molecules expressed by endothelial cells and in...

    journal_title:Current cancer drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1568009033481741

    authors: Fonsatti E,Sigalotti L,Arslan P,Altomonte M,Maio M

    更新日期:2003-12-01 00:00:00

  • Is there a Role for Epigenetic Enhancement of Immunomodulatory Approaches to Cancer Treatment?

    abstract::The efficacy of cancer immunotherapy relies on the ability of the host immune system to recognise the cancer as non-self and eliminate it from the body. Whilst this is an extremely fertile area of medical research, with positive clinical trials showing durable responses, attention must be paid to the subset of patient...

    journal_title:Current cancer drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1568009617666170206105131

    authors: Flower KJ,Ghaem-Maghami S,Brown R

    更新日期:2018-01-01 00:00:00

  • Transcription factors: molecular targets for prostate cancer intervention by phytochemicals.

    abstract::With increasing incidence of cancer at most of the sites, and growing economic burden and associated psychological and emotional trauma, it is becoming clearer that more efforts are needed for cancer cure. Since most of the chemotherapeutic drugs are non-selective because they are also toxic to the normal cells, new a...

    journal_title:Current cancer drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/156800907780809732

    authors: Kaur M,Agarwal R

    更新日期:2007-06-01 00:00:00

  • A cross-talk between NFAT and NF-κB pathways is crucial for nickel-induced COX-2 expression in Beas-2B cells.

    abstract::Cyclooxygenase-2 (COX-2) is a critical enzyme implicated in chronic inflammation-associated cancer development. Our studies have shown that the exposure of Beas-2B cells, a human bronchial epithelial cell line, to lung carcinogenic nickel compounds results in increased COX-2 expression. However, the signaling pathways...

    journal_title:Current cancer drug targets

    pub_type: 杂志文章

    doi:10.2174/156800911795656001

    authors: Cai T,Li X,Ding J,Luo W,Li J,Huang C

    更新日期:2011-06-01 00:00:00

  • Small molecule antagonists of the MDM2 oncoprotein as anticancer agents.

    abstract::In this early phase of the new era of molecularly targeted patient friendly cancer chemotherapy, there is a need for novel viable anticancer molecular targets. The MDM2 oncoprotein has been validated as a potential target for cancer drug development. MDM2 amplification and/or overexpression occur in a wide variety of ...

    journal_title:Current cancer drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1568009053332672

    authors: Buolamwini JK,Addo J,Kamath S,Patil S,Mason D,Ores M

    更新日期:2005-02-01 00:00:00

  • Targeted therapies in non-small cell lung cancer: proven concepts and unfulfilled promises.

    abstract::Targeted therapies focus on signaling pathways in cancer cells and other molecular processes involved in oncogenesis. Recent approaches affect the following major groups: the epidermal growth factor receptor (EGFR)-family, angiogenesis, the eicosanoid pathway, the PKC/ Ras/ MAPK pathway, the proteasome and inducers of...

    journal_title:Current cancer drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/156800906777441780

    authors: Auberger J,Loeffler-Ragg J,Wurzer W,Hilbe W

    更新日期:2006-06-01 00:00:00

  • Microfilament actin remodeling as a potential target for cancer drug development.

    abstract::Actin was first identified in non-muscle cells only about three decades ago, and at about the same time, it was found that actin filaments were disrupted in the malignant transformed cells. The actin network is a rather complex, yet important structural and functional system of all eukaryotic cells. Actin filaments pr...

    journal_title:Current cancer drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1568009043332998

    authors: Rao J,Li N

    更新日期:2004-06-01 00:00:00

  • The anti-tumor effect and mechanisms of action of penta-acetyl geniposide.

    abstract::Gardenia, the fruit of Gardenia jasminoides Ellis, has been widely used to treat liver and gall bladder disorders in Chinese medicine. It has been shown recently that geniposide, the main ingredient of Gardenia Fructus, exhibits the anti-tumor effect. In this review, we discuss the anti-tumor effect and possible mecha...

    journal_title:Current cancer drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1568009054064633

    authors: Peng CH,Huang CN,Wang CJ

    更新日期:2005-06-01 00:00:00

  • A molecular signature for oncogenic BRAF in human colon cancer cells is revealed by microarray analysis.

    abstract::Sporadic colorectal cancer develops through a number of functional mutations. Key events are mutually exclusive mutations in BRAF or RAS oncogenes. Signatures for BRAF oncogene have been revealed in melanoma. In a previous study we have reported a molecular signature for HRAS and KRAS mutations in colorectal cell line...

    journal_title:Current cancer drug targets

    pub_type: 杂志文章

    doi:10.2174/156800912802429364

    authors: Joyce T,Oikonomou E,Kosmidou V,Makrodouli E,Bantounas I,Avlonitis S,Zografos G,Pintzas A

    更新日期:2012-09-01 00:00:00

  • EGFR-targeting monoclonal antibodies in head and neck cancer.

    abstract::The epidermal growth factor (EGFR) and its receptor were discovered nearly 40 years ago. Over the past decade interruption of this pathway has been exploited in the treatment of various solid tumors. Antibodies that interfere with ligand binding to and dimerization of the EGFR (and small molecules that inhibit the EGF...

    journal_title:Current cancer drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/156800907782418365

    authors: Astsaturov I,Cohen RB,Harari P

    更新日期:2007-11-01 00:00:00

  • HER-2 signaling and inhibition in breast cancer.

    abstract::Amplification of the HER-2 gene occurs in approximately 25% of breast cancers, causing up-regulation of key signaling pathways which control cell growth and survival. In breast cancer patients, HER-2 overexpression correlates with an aggressive phenotype and poor prognosis. HER-2, therefore, has become the focus of ma...

    journal_title:Current cancer drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/156800909788166484

    authors: Browne BC,O'Brien N,Duffy MJ,Crown J,O'Donovan N

    更新日期:2009-05-01 00:00:00

  • Targeting IDH Mutations in AML: Wielding the Double-edged Sword of Differentiation.

    abstract::The genomic characterization of acute myeloid leukemia (AML) by DNA sequencing has illuminated subclasses of the disease, with distinct driver mutations, that might be responsive to targeted therapies. Approximately 15-23% of AML genomes harbor mutations in one of two isoforms of isocitrate dehydrogenase (IDH1 or IDH2...

    journal_title:Current cancer drug targets

    pub_type: 杂志文章

    doi:10.2174/1568009620666200424145622

    authors: Becker JS,Fathi AT

    更新日期:2020-01-01 00:00:00

  • Endothelial progenitor cells: hope beyond controversy.

    abstract::The capacity to induce new blood vessel formation or to repair damaged vessels is an attractive idea that has, for a long time, captured the attention and imagination of researchers. Beside the identification of the pro-angiogenic growth factors and their counterpart inhibitors, the discovery of endothelial progenitor...

    journal_title:Current cancer drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/156800910793358041

    authors: Pasquier E,Dias S

    更新日期:2010-12-01 00:00:00

  • Adding to the mix: fibroblast growth factor and platelet-derived growth factor receptor pathways as targets in non-small cell lung cancer.

    abstract::The treatment of advanced non � small cell lung cancer (NSCLC) increasingly involves the use of molecularly targeted therapy with activity against either the tumor directly, or indirectly, through activity against host-derived mechanisms of tumor support such as angiogenesis. The most well studied signaling pathway as...

    journal_title:Current cancer drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/156800912799095144

    authors: Kono SA,Heasley LE,Doebele RC,Camidge DR

    更新日期:2012-02-01 00:00:00

  • 11-Phenylundeca-5Z,9Z-dienoic Acid: Stereoselective Synthesis and Dual Topoisomerase I/IIα Inhibition.

    abstract::(5Z,9Z)-11-Phenylundeca-5,9-dienoic acid was stereoselectively synthesized, based on original cross-cyclomagnesiation of 2-(hepta-5,6-dien-1-yloxy)tetrahydro-2H-pyran and buta-2,3-dien-1-ylbenzene with EtMgBr in the presence of the Cp2TiCl2 catalyst giving 2,5-dialkylydenemagnesacyclopentane in 86% yield. The acid hyd...

    journal_title:Current cancer drug targets

    pub_type: 杂志文章

    doi:10.2174/1568009615666150506093155

    authors: D'yakonov VA,Dzhemileva LU,Makarov AA,Mulyukova AR,Baevd DS,Khusnutdinova EK,Tolstikova TG,Dzhemilev UM

    更新日期:2015-01-01 00:00:00

  • UDP-N-acetyl-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase- 6 (pp-GalNAc-T6): Role in Cancer and Prospects as a Drug Target.

    abstract::UDP-N-acetyl-D-galactosamine: polypeptide N-acetylgalactosaminyl transferase-6 (pp-GalNAc-T6) is a member of the N-acetyl-D-galactosamine transferase family. It catalyzes the addition of N-acetyl-D-galactosamine to proteins, often the first step in O-glycosylation of proteins. Glycosylated proteins play important role...

    journal_title:Current cancer drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1568009616666160922102641

    authors: Banford S,Timson DJ

    更新日期:2017-01-01 00:00:00

  • Voltage-dependent potassium channels Kv1.3 and Kv1.5 in human cancer.

    abstract::Membrane ion channels participate in cancerous processes such as proliferation, migration and invasion, which contribute to metastasis. Increasing evidence indicates that voltage-dependent K(+) (Kv) channels are involved in the proliferation of many types of cells, including tumor cells. Kv channels have generated imm...

    journal_title:Current cancer drug targets

    pub_type: 杂志文章

    doi:10.2174/156800909790192400

    authors: Bielanska J,Hernández-Losa J,Pérez-Verdaguer M,Moline T,Somoza R,Ramón Y Cajal S,Condom E,Ferreres JC,Felipe A

    更新日期:2009-12-01 00:00:00

  • Role of the RAS in pancreatic cancer.

    abstract::Angiotensin II (Ang II), a main effector peptide of the renin-angiotensin system (RAS), mediates a hormonal action in the maintenance of blood pressure and electrolyte levels, and thus fluid homeostasis. Ang II also mediates paracrine, autocrine and/or intracrine actions in the control of various specific functions of...

    journal_title:Current cancer drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/156800911795538110

    authors: Lau ST,Leung PS

    更新日期:2011-05-01 00:00:00

  • Oncolytic viruses driven by tumor-specific promoters.

    abstract::Oncolytic viruses can selectively replicate in and lead to tumor cell lysis with minimal infection/replication potential in adjoining non-neoplastic tissue. Because of paramount safety concerns, first-generation oncolytic viruses were designed to be significantly attenuated in their lytic potential. Results from recen...

    journal_title:Current cancer drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/156800907780058880

    authors: Hardcastle J,Kurozumi K,Chiocca EA,Kaur B

    更新日期:2007-03-01 00:00:00

  • Formulation, Pharmacokinetic Evaluation and Cytotoxicity of an Enhanced- penetration Paclitaxel Nanosuspension.

    abstract:BACKGROUND:Improving poorly soluble drugs into druggability was a major problem faced by pharmaceutists. Nanosuspension can improve the druggability of insoluble drugs by improving the solubility, chemical stability and reducing the use of additives, which provided a new approach for the development and application of ...

    journal_title:Current cancer drug targets

    pub_type: 杂志文章

    doi:10.2174/1568009618666180629150927

    authors: Cao Y,Wei Z,Li M,Wang H,Yin L,Chen D,Wang Y,Chen Y,Yuan Q,Pu X,Zong L,Duan S

    更新日期:2019-01-01 00:00:00

  • Targeting ATP7A to increase the sensitivity of neuroblastoma cells to retinoid therapy.

    abstract::Following the discovery that defective retinoid signaling directly contributes to tumorigenesis, and, that retinoids have an anti-cancer effect in vitro and in vivo, retinoids have become part of the routine care in children with neuroblastoma at the stage of minimal residual disease. However, many patients still rela...

    journal_title:Current cancer drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/156800911796798968

    authors: Cheung BB,Marshall GM

    更新日期:2011-09-01 00:00:00

  • Targeting of Hsp32 in solid tumors and leukemias: a novel approach to optimize anticancer therapy.

    abstract::Heat shock protein 32 (Hsp32), also known as heme oxygenase-1 (HO-1), is a stress-related anti-apoptotic molecule, that has been implicated in enhanced survival of neoplastic cells and in drug-resistance. We here show that Hsp32 is expressed in most solid tumors and hematopoietic neoplasms and may be employed as a new...

    journal_title:Current cancer drug targets

    pub_type: 杂志文章

    doi:10.2174/156800909789057024

    authors: Gleixner KV,Mayerhofer M,Vales A,Gruze A,Hörmann G,Cerny-Reiterer S,Lackner E,Hadzijusufovic E,Herrmann H,Iyer AK,Krauth MT,Pickl WF,Marian B,Panzer-Grümayer R,Sillaber C,Maeda H,Zielinski C,Valent P

    更新日期:2009-08-01 00:00:00

  • Lipid-based Nanoplatforms in Cancer Therapy: Recent Advances and Applications.

    abstract::Though modern available cancer therapies are effective, they possess major adverse effects, causing non-compliance to patients. Furthermore, the majority of the polymeric-based medication platforms are certainly not universally acceptable, due to their several restrictions. With this juxtaposition, lipid-based medicat...

    journal_title:Current cancer drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1568009620666200115160805

    authors: Rajpoot K

    更新日期:2020-01-01 00:00:00

  • The SCF-type E3 Ubiquitin Ligases as Cancer Targets.

    abstract::The ubiquitin system controls protein stability and function. F-box proteins form SCF (SKP1-Cullin1-F-box protein)-type ubiquitin (E3) ligases to selectively target their substrates for degradation via the ubiquitin-proteasome pathway. Here, we review F-box proteins associated with cancer development. S-phase kinase-a...

    journal_title:Current cancer drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1568009616666151112122231

    authors: Kitagawa K,Kitagawa M

    更新日期:2016-01-01 00:00:00

  • OncomicroRNAs-Mediated Tumorigenesis: Implication in Cancer Diagnosis and Targeted Therapy.

    abstract::MicroRNAs (miRNAs) control the expression of approximately 60% of protein-coding genes and regulate cell metabolism, proliferation, differentiation, and apoptosis. Notably, aberrant expression of miRNAs contributes to several diseases including cancer. Accumulating evidence indicates that miRNAs play important roles i...

    journal_title:Current cancer drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1568009616666160216130608

    authors: Zheng N,Yang P,Wang Z,Zhou Q

    更新日期:2017-01-01 00:00:00

  • Arsenic trioxide exerts anti-lung cancer activity by inhibiting angiogenesis.

    abstract::Arsenic trioxide (As2O3) has been used in the clinic for the treatment of acute promyelocytic 1eukemia and some solid tumors. However, its effectiveness against lung cancer has not been well demonstrated, and the underlying mechanism(s) of action remain unclear. In the present study, we found that As2O3 significantly ...

    journal_title:Current cancer drug targets

    pub_type: 杂志文章

    doi:10.2174/1568009614666140725090000

    authors: Yang MH,Zang YS,Huang H,Chen K,Li B,Sun GY,Zhao XW

    更新日期:2014-01-01 00:00:00