In-vitro and in-vivo anti-cancer activity of a novel gemcitabine-cardiolipin conjugate.

Abstract:

:Our objectives were to study the biological activity of a novel gemcitabine-cardiolipin conjugate (NEO6002) and compare that with gemcitabine. Cytotoxicity in vitro was determined against several gemcitabine-sensitive parental and gemcitabine-resistant cancer cell lines using the sulforhodamine B assay. The in vivo toxicity was examined by changes in body weight and hematologic indices of conventional mice. Immunodeficient SCID mice bearing P388 and BxPC-3 tumor xenografts were used to evaluate the in-vivo therapeutic efficacy. Both NEO6002 and gemcitabine showed pro-apoptotic and cytotoxic effects against all gemcitabine-sensitive cell lines tested. Unlike gemcitabine, the cytotoxicity of NEO6002 was independent of nucleoside transporter (NT) inhibitors, indicating a different internalization route of NEO6002. The conjugate demonstrated a favorable activity not only in ARAC-8C, a NT-deficient gemcitabine-resistant human leukemia cell line, but also in several other gemcitabine-resistant cell lines. At the in-vivo level, a comparative toxicity study showed a significant body weight loss and a decrease in white blood cell counts in gemcitabine-treated mice, whereas the influence of NEO6002 was mild. Treatment of NEO6002 at 27 micromol/kg increased the median survival of CD2F1 mice bearing P388 cells by up to 73%, while at the same doses and schedule of gemcitabine resulted in toxic deaths of all treated mice. At a dose of 18 micromol/kg, NEO6002 inhibited the growth of BxPC-3 xenografts by 52%, while only 32% of tumor inhibition was achieved with gemcitabine. We conclude that NEO6002 may be an effective chemotherapeutic agent with improved tolerability and can potentially circumvent NT-deficient, gemcitabine-resistant tumors.

journal_name

Anticancer Drugs

journal_title

Anti-cancer drugs

authors

Chen P,Chien PY,Khan AR,Sheikh S,Ali SM,Ahmad MU,Ahmad I

doi

10.1097/01.cad.0000185182.80227.48

subject

Has Abstract

pub_date

2006-01-01 00:00:00

pages

53-61

issue

1

eissn

0959-4973

issn

1473-5741

pii

00001813-200601000-00007

journal_volume

17

pub_type

杂志文章
  • Proceedings of the First International Conference on PEP005.

    abstract::The sap of Euphorbia peplus, commonly know as 'petty spurge', 'radium weed' or 'milkweed' has been used for centuries as a traditional treatment for skin conditions, including warts, corns and cancers of the skin. Documentation of its use by medical professionals to treat basal cell carcinoma (BCC) dates from the earl...

    journal_title:Anti-cancer drugs

    pub_type:

    doi:10.1097/CAD.0b013e3280149ec5

    authors: Ogbourne SM,Hampson P,Lord JM,Parsons P,De Witte PA,Suhrbier A

    更新日期:2007-03-01 00:00:00

  • In vitro targeting of a cytotoxic analog of luteinizing hormone-releasing hormone AN-207 to ES-2 human ovarian cancer cells as demonstrated by microsatellite analyses.

    abstract::Targeting of cytotoxic agents represents a modern approach to the treatment of various cancers, that improves the efficacy and reduces peripheral toxicity. Recently we developed a powerful cytotoxic analog of luteinizing hormone-releasing hormone (LHRH), AN-207, designed to be targeted to tumors that express LHRH rece...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/00001813-200101000-00010

    authors: Arencibia JM,Schally AV,Halmos G,Nagy A,Kiaris H

    更新日期:2001-01-01 00:00:00

  • TUG1 knockdown inhibits the tumorigenesis and progression of prostate cancer by regulating microRNA-496/Wnt/β-catenin pathway.

    abstract::Our study aimed to further investigate the roles and molecular mechanisms of lncRNA taurine upregulated gene 1 (TUG1) in the development and progression of PC. RT-qPCR assay was carried out to measure expression of TUG1, miR-496, together with β-catenin, cyclin D1 and c-myc. Protein levels of β-catenin, cyclin D1 and ...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0000000000000882

    authors: Li G,Yang J,Chong T,Huang Y,Liu Y,Li H

    更新日期:2020-07-01 00:00:00

  • Investigation of cellular mechanisms involved in apoptosis induced by a synthetic naphthylchalcone in acute leukemia cell lines.

    abstract::We have previously reported the cytotoxic effects of chalcone A1, derived from 1-naphthaldehyde, in leukemia cell lines. On the basis of these findings, the main aim of this study was to elucidate some of the molecular mechanisms involved in apoptosis induced by chalcone A1 toward K562 and Jurkat cells. In both cell l...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0000000000000384

    authors: Maioral MF,Moraes AC,Sgambatti KR,Mascarello A,Chiaradia-Delatorre LD,Yunes RA,Nunes RJ,Santos da Silva MC

    更新日期:2016-09-01 00:00:00

  • Effects of oxymatrine on the apoptosis and proliferation of gallbladder cancer cells.

    abstract::Gallbladder carcinoma is the most common malignancy of the biliary tract and is associated with a very poor outcome. The aim of the present study was to investigate the effects of oxymatrine (OM) on gallbladder cancer cells and the possible mechanism of its effects. The effects of OM on the proliferation of gallbladde...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0000000000000124

    authors: Wu XS,Yang T,Gu J,Li ML,Wu WG,Weng H,Ding Q,Mu JS,Bao RF,Shu YJ,Cao Y,Wang XA,Ding QC,Dong P,Xie SF,Liu YB

    更新日期:2014-10-01 00:00:00

  • Modulation of melphalan cytotoxic activity in human melanoma cell lines.

    abstract::The aim of the present study was to potentiate the cytotoxic effects of melphalan through pharmacological and physical modulators. The combination of the cytotoxic agent with ethacrynic acid, a glutathione-S-transferase pi (GST pi) inhibitor, or topotecan, a topoisomerase I inhibitor, or mild hyperthermia was investig...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/00001813-199607000-00017

    authors: Supino R,Caserini C,Orlandi L,Zaffaroni N,Silvestrini R,Vaglini M,Zunino F

    更新日期:1996-07-01 00:00:00

  • Preclinical antitumor efficacy evaluation of dendrimer-based methotrexate conjugates.

    abstract::Our previous studies have demonstrated the in-vitro and in-vivo targeting of a generation-5 (G5) dendrimer-based multifunctional conjugate, which used folic acid (FA) as the targeting agent and methotrexate (MTX) as the chemotherapeutic drug. For the synthesized G5-FA-MTX nanodevice conjugate to be clinically applicab...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0b013e3282f28842

    authors: Myc A,Douce TB,Ahuja N,Kotlyar A,Kukowska-Latallo J,Thomas TP,Baker JR Jr

    更新日期:2008-02-01 00:00:00

  • Adverse events in patients with liver cancer.

    abstract::This study aimed to further the understanding of the incidence of adverse events (AEs) in a population-based representative liver cancer population where there is currently a lack of knowledge. We carried out a retrospective cohort study using data from an administrative claims database between 1 January 2004 and 31 D...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0b013e3283607f4f

    authors: Dreyfus B,Kawabata HM,Gomez-Caminero A

    更新日期:2013-07-01 00:00:00

  • Anticancer activities of alkylating pyrrole-imidazole polyamides with specific sequence recognition.

    abstract::In recent years, many diseases including cancer and hereditary and viral diseases have been understood at the DNA sequence level. Direct control of the expression level of a specific gene would provide a promising approach for knowledge-based therapy. N-methylpyrrole and N-methylimidazole polyamides are a new type of ...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章,评审

    doi:10.1097/CAD.0b013e328334d8f9

    authors: Shinohara K,Bando T,Sugiyama H

    更新日期:2010-03-01 00:00:00

  • No evidence of tumor growth stimulation in human tumors in vitro following treatment with recombinant human growth hormone.

    abstract::In a recent study we demonstrated that recombinant human growth hormone (r-hGH; Saizen) delayed tumor-induced cachexia in human tumor xenografts in vivo. Such a therapeutic effect could have a great impact in the supportive care of advanced cancer patients. Before large clinical studies are initiated possible growth s...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/00001813-200009000-00011

    authors: Fiebig HH,Dengler W,Hendriks HR

    更新日期:2000-09-01 00:00:00

  • Binding and internalization of NGR-peptide-targeted liposomal doxorubicin (TVT-DOX) in CD13-expressing cells and its antitumor effects.

    abstract::In an effort to develop new agents and molecular targets for the treatment of cancer, aspargine-glycine-arginine (NGR)-targeted liposomal doxorubicin (TVT-DOX) is being studied. The NGR peptide on the surface of liposomal doxorubicin (DOX) targets an aminopeptidase N (CD13) isoform, specific to the tumor neovasculatur...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0b013e3282a213ce

    authors: Garde SV,Forté AJ,Ge M,Lepekhin EA,Panchal CJ,Rabbani SA,Wu JJ

    更新日期:2007-11-01 00:00:00

  • Are there benefits in routine clinical practice of continuing trastuzumab after progression for metastatic breast cancer patients?

    abstract::The efficacy of trastuzumab beyond metastatic disease progression (PD) is controversial. We retrospectively analyzed 213 patients with HER2-positive metastatic breast cancer treated with trastuzumab-based therapies between November 1998 and December 2010. Out of 213 patients, 134 (58%) had received trastuzumab consecu...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0b013e32835679d3

    authors: Esposito A,Munzone E,Bagnardi V,Adamoli L,Sciandivasci A,Cullurà D,Goldhirsch A,Nolè F

    更新日期:2012-11-01 00:00:00

  • Tamoxifen and epigallocatechin gallate are synergistically cytotoxic to MDA-MB-231 human breast cancer cells.

    abstract::High concentrations of specific catechins [epigallocatechin gallate (EGCG), epigallocatechin (EGC) and epicatechin gallate (ECG)] inhibit the proliferation of many different cancer cell lines. The aim of this work was to determine if low concentrations of catechins with and without 4-hydroxytamoxifen (4-OHT) co-treatm...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/00001813-200410000-00010

    authors: Chisholm K,Bray BJ,Rosengren RJ

    更新日期:2004-10-01 00:00:00

  • Inhibition of NADPH oxidase protects against metastasis of human lung cancer by decreasing microRNA-21.

    abstract::The objective of this study was to detect the effect of NADPH oxidase (NOX) inhibition on metastasis of lung cancer. Primary human lung cancer cells were isolated from surgical tissues using the Cancer Cell Isolation Kit. Invasion was detected using the BD Biocoat Matrigel Invasion Chamber assay. Expressions of microR...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0000000000000198

    authors: Yan S,Liu G,Pei C,Chen W,Li P,Wang Q,Jin X,Zhu J,Wang M,Liu X

    更新日期:2015-04-01 00:00:00

  • Effect of gastric pH on erlotinib pharmacokinetics in healthy individuals: omeprazole and ranitidine.

    abstract::The aim of this study was to evaluate the effect of coadministration of acid-reducing agents on the pharmacokinetic exposure of orally administered epidermal growth factor receptor inhibitor erlotinib, a drug that displays pH-dependent solubility. Two studies were conducted, the first with the proton pump inhibitor om...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章,随机对照试验

    doi:10.1097/CAD.0000000000000212

    authors: Kletzl H,Giraudon M,Ducray PS,Abt M,Hamilton M,Lum BL

    更新日期:2015-06-01 00:00:00

  • Targeting urokinase-type plasminogen activator and its receptor for cancer therapy.

    abstract::Cancer invasion and metastasis are highly complex processes and a serine protease urokinase-type plasminogen activator/urokinase-type plasminogen activator receptor system has been postulated to play a central role in the mediation of cancer progression. Of note, malignant tumor urokinase-type plasminogen activator an...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章,评审

    doi:10.1097/01.cad.0000231483.09439.3a

    authors: Nozaki S,Endo Y,Nakahara H,Yoshizawa K,Ohara T,Yamamoto E

    更新日期:2006-11-01 00:00:00

  • [Multi-targeted antifolate therapy roe non-small cell lung cancer and mesothelioma].

    abstract::Multi-targeted antifolate (MTA) is an anti-metabolite with useful activity in the treatment of non-operable patients presenting with non-small cell lung cancer. Its good efficacy and tolerability profile as first-line therapy was demonstrated in phase II studies of MTA as monotherapy. The use of MTA as second-line the...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章,评审

    doi:

    authors: Le Chevallier T

    更新日期:2001-07-01 00:00:00

  • Phase I-II evaluation of intravesical novantrone (mitoxantrone) in superficial bladder cancer.

    abstract::The objective of this study was to determine the safety and efficacy of intravesical novantrone in refractory superficial bladder cancer. The eligibility criteria included proven carcinoma in situ or superficial transitional cell carcinoma of the bladder at stage Ta or T1 that was proven refractory to or in relapse af...

    journal_title:Anti-cancer drugs

    pub_type: 临床试验,杂志文章

    doi:10.1097/00001813-199104000-00005

    authors: Sharifi R,Lee M,Clayton M,Lamb D,Siami P,Strub M,Albert D,Sarosdy M

    更新日期:1991-04-01 00:00:00

  • Cellular pharmacology of the combination of oxaliplatin with topotecan in the IGROV-1 human ovarian cancer cell line.

    abstract::The clinical development of combinations of cisplatin or carboplatin with DNA topoisomerase I (Topo I) inhibitors is based on their overlapping spectrum of antitumor activity and their in vitro synergy, but is limited by significant hematotoxicity. We studied the cellular interactions between oxaliplatin and topotecan...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/00001813-199902000-00008

    authors: Goldwasser F,Bozec L,Zeghari-Squalli N,Misset JL

    更新日期:1999-02-01 00:00:00

  • Characterization by flow cytometry and fluorescein-methotrexate labeling of hydrophilic and lipophilic antifolate resistance in cultured mammalian cells.

    abstract::The aim of this review is to summarize currently available information on the rapid screening and initial characterization of the different mechanisms of resistance to hydrophilic [e.g. methotrexate (MTX)] and lipophilic antifolates [e.g. trimetrexate (TMTX)] in cultured mammalian cells using fluorescein-methotrexate ...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章,评审

    doi:10.1097/00001813-199310000-00002

    authors: Assaraf YG

    更新日期:1993-10-01 00:00:00

  • In-vitro antiproliferative activities and kinase inhibitory potencies of meridianin derivatives.

    abstract::Marine alkaloid meridianin G derivatives, substituted on the pyrimidine ring by aryl groups, were evaluated for their kinase inhibitory potencies and their in-vitro antiproliferative activities. The derivatives were tested toward a panel of nine protein kinases (KDR, IGF-1R, c-Met, RET, c-Src, c-Abl, PKA, CDK2/cyclin ...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0b013e32830ce4d8

    authors: Rossignol E,Debiton E,Fabbro D,Moreau P,Prudhomme M,Anizon F

    更新日期:2008-09-01 00:00:00

  • Aspirin reduces adverse effects of gefitinib.

    abstract::We measured serum levels of soluble (s) P-selectin and thromboxane B2 (TxB2) in patients with lung cancer treated with gefitinib, and investigated the effect of low-dose aspirin on some adverse effects of gefitinib. The serum levels of sP-selectin and TxB2 increased significantly in all patients who received gefitinib...

    journal_title:Anti-cancer drugs

    pub_type: 临床试验,杂志文章

    doi:10.1097/01.cad.0000203385.45163.76

    authors: Kanazawa S,Yamaguchi K,Kinoshita Y,Muramatsu M,Komiyama Y,Nomura S

    更新日期:2006-04-01 00:00:00

  • Chemosensitization and drug accumulation effects of VX-710, verapamil, cyclosporin A, MS-209 and GF120918 in multidrug resistant HL60/ADR cells expressing the multidrug resistance-associated protein MRP.

    abstract::Overexpression of the multidrug resistance MDR1 gene product P-glycoprotein and/or the multidrug resistance-associated protein MRP confers multidrug resistance to cancer cells. The pipecolinate derivative VX-710 has previously been demonstrated to reverse MDR1-mediated multidrug resistance at concentrations of 0.5-2.5...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/00001813-199702000-00005

    authors: Germann UA,Ford PJ,Shlyakhter D,Mason VS,Harding MW

    更新日期:1997-02-01 00:00:00

  • In-vitro cytotoxicity of ET-743 (Trabectedin, Yondelis), a marine anti-cancer drug, in the Hep G2 cell line: influence of cytochrome P450 and phase II inhibition, and cytochrome P450 induction.

    abstract::ET-743 is a marine anti-cancer drug and is currently in phase I trials in which the effect of combination therapies will be investigated. Its dose-limiting toxicity in patients is hepatotoxicity. In-vitro studies have shown that ET-743 is mainly metabolized by cytochrome P450 (CYP) 3A4, but also by 2C9, 2C19, 2D6 and ...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/01.cad.0000180121.16407.38

    authors: Brandon EF,Meijerman I,Klijn JS,den Arend D,Sparidans RW,Lázaro LL,Beijnen JH,Schellens JH

    更新日期:2005-10-01 00:00:00

  • Phthalimide analogs of CB 1954: synthesis and bioactivation.

    abstract::Four novel 4-substituted 5-nitrophthalimides (5-substituted-6-nitro-1,3-dihydro-isoindol-1,3-diones), 6, 7, 10 and 11, and the known 5 are prepared as analogs of the dinitrobenzamide prodrug CB 1954, 1, and considered as potential candidates for gene-directed enzyme prodrug therapy. All the phthalimides are poor subst...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/00001813-199909000-00011

    authors: Mehta LK,Hobbs S,Chen S,Knox RJ,Parrick J

    更新日期:1999-09-01 00:00:00

  • The effect of imatinib mesylate (Glivec) on human tumor-derived cells.

    abstract::Imatinib mesylate is a specific inhibitor of the Bcr-Abl protein tyrosine kinase that competes with ATP for its specific binding site in the kinase domain. It has activity against platelet-derived growth factor receptor alpha and beta (PDGFR-alpha and -beta), and c-kit, the receptor for stem cell factor. We have used ...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/01.cad.0000215062.16308.41

    authors: Knight LA,Di Nicolantonio F,Whitehouse PA,Mercer SJ,Sharma S,Glaysher S,Hungerford JL,Hurren J,Lamont A,Cree IA

    更新日期:2006-07-01 00:00:00

  • The TYMS-TSER polymorphism is associated with toxicity of low-dose capecitabine in patients with advanced gastrointestinal cancer.

    abstract::Low doses of drugs delivered at close, regular intervals are increasingly being used to manage patients with different neoplasms. Despite the good tolerability, treatment-related adverse events still occur following metronomic protocols. The aim of this study was to retrospectively investigate whether polymorphisms of...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0000000000000429

    authors: Romiti A,Roberto M,D'Antonio C,Onesti CE,Barucca V,Milano A,Gentile G,Lionetto L,Medda E,Mazzuca F,Botticelli A,Falcone R,Simmaco M,Marchetti P

    更新日期:2016-11-01 00:00:00

  • In vitro pharmacokinetic study of the novel anticancer agent E7070: red blood cell and plasma protein binding in human blood.

    abstract::E7070 is a novel sulfonamide anticancer agent that arrests the G(1)/S phase of the cell cycle. Preclinical and phase I studies have demonstrated non-linear pharmacokinetics (PK) of the drug. A population PK analysis revealed that the human plasma concentration-time data were best described by a three-compartment model...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/00001813-200307000-00003

    authors: Bongard HJ,Pluim D,Waardenburg RC,Ravic M,Beijnen JH,Schellens JH

    更新日期:2003-07-01 00:00:00

  • Chitosan nanoparticles for dermaseptin peptide delivery toward tumor cells in vitro.

    abstract::The present study aimed to entrap and characterize the morphology and antitumor effects of a dermaseptin (DStomo01) peptide in chitosan nanoparticles, in vitro. DStomo01 nanoparticles showed moderate polydispersivity, excellent colloidal stability, and slow release. It was noted that free DStomo01 induced DNA fragment...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0000000000000052

    authors: Medeiros KA,Joanitti GA,Silva LP

    更新日期:2014-03-01 00:00:00

  • Generation of DNA damage by anti-neoplastic agents.

    abstract::DNA has been one of the major targets of cancer chemotherapy. A variety of anti-neoplastic agents can cause different types of DNA lesions, including base alterations, single- or double-strand DNA breaks, DNA-DNA cross-links and DNA-protein cross-links. The exact processes by which these DNA lesions lead to cell death...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章,评审

    doi:10.1097/00001813-199112000-00003

    authors: Kubota M

    更新日期:1991-12-01 00:00:00