MT119, a new planar-structured compound, targets the colchicine site of tubulin arresting mitosis and inhibiting tumor cell proliferation.

Abstract:

:Microtubule-targeted drugs are now indispensable for the therapy of various cancer types worldwide. In this article, we report MT119 [6-[2-(4-methoxyphenyl) -ethyl]-9-[(pyridine-3-ylmethyl)amino]pyrido[2',1':2,3]imida-zo[4,5-c]isoquinolin-5(6H)-one] as a new microtubule-targeted agent. MT119 inhibited tubulin polymerization significantly both in tumor cells and in cell-free systems, which was followed by the disruption of mitotic spindle assembly. Surface plasmon resonance-based analyses showed that MT119 bound to purified tubulin directly, with the K(D) value of 10.6 μM. The binding of MT119 in turn caused tubulin conformational changes as evidenced by the quenched tryptophan fluorescence, the reduction of the bis-ANS reactivity and the decreased DTNB-sulfhydryl reaction rate. Competitive binding assays further revealed that MT119 bound to tubulin at its colchicine site. Consequently, by inhibiting tubulin polymerization, MT119 arrested different tumor cells at mitotic phase, which contributed to its potent antitumor activity in vitro. MT119 was also similarly cytotoxic to vincristine-, adriamycin- or mitoxantrone-resistant cancer cells and to their corresponding parental cells. Together, these data indicate that MT119 represents a new class of colchicine-site-targeted inhibitors against tubulin polymerization, which might be a promising starting point for future cancer therapeutics.

journal_name

Int J Cancer

authors

Zhang Z,Meng T,Yang N,Wang W,Xiong B,Chen Y,Ma L,Shen J,Miao ZH,Ding J

doi

10.1002/ijc.25661

subject

Has Abstract

pub_date

2011-07-01 00:00:00

pages

214-24

issue

1

eissn

0020-7136

issn

1097-0215

journal_volume

129

pub_type

杂志文章
  • Properties of reticulum-cell sarcomas in SJL/J mice. I. Proliferative response to tumor cells of T-derived lymphoid cells from normal mice.

    abstract::Cells from reticulum-cell sarcomas (RCS), tumors with a probable B-cell origin in the SJL/J mouse strain, induced a high degree of proliferation in O-bearing syngeneic lymph-node and thymus cells obtained from young non-tumours mice. Although of considerably lower magnitude, a proliferation of SJL/J thymus cells to sy...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910140615

    authors: Lerman SP,Chapman JM,Carswell EA,Thorbecke GJ

    更新日期:1974-12-15 00:00:00

  • The combination of epigallocatechin gallate and curcumin suppresses ER alpha-breast cancer cell growth in vitro and in vivo.

    abstract::Both epigallocatechin gallate (EGCG) and curcumin have shown efficacy in various in vivo and in vitro models of cancer. This study was designed to determine the efficacy of these naturally derived polyphenolic compounds in vitro and in vivo, when given in combination. Studies in MDA-MB-231 cells demonstrated that EGCG...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.23328

    authors: Somers-Edgar TJ,Scandlyn MJ,Stuart EC,Le Nedelec MJ,Valentine SP,Rosengren RJ

    更新日期:2008-05-01 00:00:00

  • Expression and functional activity of fibroblast growth factors and their receptors in human pancreatic cancer.

    abstract::We have analysed expression of the first 7 members of the family of heparin-binding fibroblast growth factor (FGFs) and their 4 high-affinity receptors (FGFRs) in human pancreatic carcinoma cell lines, both at the mRNA and protein levels. In cell lines expressing FGFRs, 2 typical patterns were observed: (i) expression...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910590515

    authors: Leung HY,Gullick WJ,Lemoine NR

    更新日期:1994-12-01 00:00:00

  • Mutation analysis of the N-ras proto-oncogene in active and remission phase of human acute leukemias.

    abstract::DNA isolated from blood or bone-marrow samples from 18 patients with acute non-lymphocytic leukemia (ANLL) and 14 patients with acute lymphocytic leukemia (ALL) was analyzed for the presence of mutations in the N-ras gene. Using synthetic oligonucleotide probes we detected mutations in 5 cases of ANLL; 4 GGT----GAT tr...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910410112

    authors: Senn HP,Trân-Thang C,Wodnar-Filipowicz A,Jiricny J,Fopp M,Gratwohl A,Signer E,Weber W,Moroni C

    更新日期:1988-01-15 00:00:00

  • Dysregulated expression of transforming growth factor beta and its type-I and type-II receptors in basal-cell carcinoma.

    abstract::In mammals, transforming growth factor-beta (TGF-beta) is found in 3 highly homologous isoforms that exert their effects via heteromeric complexes of type-I and type-II receptors (TbetaR-I and TbetaR-II). TGF-beta regulates the growth and metabolism of various cell types, including keratinocytes. We have investigated ...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0215(19970516)71:4<505::aid-ijc

    authors: Furue M,Kato M,Nakamura K,Nashiro K,Kikuchi K,Okochi H,Miyazono K,Tamaki K

    更新日期:1997-05-16 00:00:00

  • Inhibition of a complement regulator in vivo enhances antibody therapy in a model of mammary adenocarcinoma.

    abstract::Membrane-bound complement regulatory proteins provide tumor cells with protection from antibody and complement in vitro. However, complement regulators are widely expressed on normal tissue, and inhibiting the function of complement regulatory proteins on tumor cells in vivo has not been investigated due to the absenc...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.20178

    authors: Imai M,Ohta R,Okada N,Tomlinson S

    更新日期:2004-07-20 00:00:00

  • Mendelian randomization analyses suggest a role for cholesterol in the development of endometrial cancer.

    abstract::Blood lipids have been associated with the development of a range of cancers, including breast, lung and colorectal cancer. For endometrial cancer, observational studies have reported inconsistent associations between blood lipids and cancer risk. To reduce biases from unmeasured confounding, we performed a bidirectio...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.33206

    authors: Kho PF,Amant F,Annibali D,Ashton K,Attia J,Auer PL,Beckmann MW,Black A,Brinton L,Buchanan DD,Chanock SJ,Chen C,Chen MM,Cheng THT,Cook LS,Crous-Bous M,Czene K,De Vivo I,Dennis J,Dörk T,Dowdy SC,Dunning AM,Dürst

    更新日期:2021-01-15 00:00:00

  • Transcriptomic profiling reveals three molecular phenotypes of adenocarcinoma at the gastroesophageal junction.

    abstract::Cancers occurring at the gastroesophageal junction (GEJ) are classified as predominantly esophageal or gastric, which is often difficult to decipher. We hypothesized that the transcriptomic profile might reveal molecular subgroups which could help to define the tumor origin and behavior beyond anatomical location. The...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.32384

    authors: Bornschein J,Wernisch L,Secrier M,Miremadi A,Perner J,MacRae S,O'Donovan M,Newton R,Menon S,Bower L,Eldridge MD,Devonshire G,Cheah C,Turkington R,Hardwick RH,Selgrad M,Venerito M,Malfertheiner P,OCCAMS Consortium.,F

    更新日期:2019-12-15 00:00:00

  • Family history of breast or ovarian cancer modifies the risk of secondary leukemia after breast cancer: results from a population-based study.

    abstract::We evaluated the impact of a family history of breast/ovarian cancer on the risk of secondary leukemia following breast cancer. At the Geneva cancer registry, we identified 4,397 patients diagnosed with invasive breast cancer between 1990 and 2004. Patients were followed up for leukemia until the end of 2005. Family h...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.23212

    authors: Verkooijen HM,Fioretta G,Rapiti E,Vlastos G,Neyroud-Caspar I,Chappuis PO,Bouchardy C

    更新日期:2008-03-01 00:00:00

  • Telomerase components as a diagnostic tool in human oral lesions.

    abstract::Telomerase activity is considered to be a diagnostic marker of malignancy since most malignant cells express this activity and most somatic cells do not. However, the detection of telomerase activity is rather complicated and is affected by many factors. Recently, human telomerase components were cloned and found to c...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0215(19990105)80:1<1::aid-ijc1>

    authors: Sumida T,Hamakawa H,Sogawa K,Sugita A,Tanioka H,Ueda N

    更新日期:1999-01-05 00:00:00

  • Circulating lncRNA SNHG11 as a novel biomarker for early diagnosis and prognosis of colorectal cancer.

    abstract::Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer mortality worldwide. Emerging evidence indicates that tumour cells release substantial amounts of RNA into the bloodstream, in which RNA strongly resists RNases and is present at sufficient levels for quantitative analyses. ...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.32747

    authors: Xu W,Zhou G,Wang H,Liu Y,Chen B,Chen W,Lin C,Wu S,Gong A,Xu M

    更新日期:2020-05-15 00:00:00

  • Immunogenicity of recombinant GA733-2E antigen (CO17-1A, EGP, KS1-4, KSA, Ep-CAM) in gastro-intestinal carcinoma patients.

    abstract::Targeting the GA733 antigen (also known as CO17-1A, EGP, KS1-4, KSA, Ep-CAM) by monoclonal antibody CO17-1A or anti-idiotypic antibodies mimicking the CO17-1A or GA733 epitope has induced prolonged survival and specific immune responses to the antigen, respectively, in colorectal cancer (CRC) patients. In pre-clinical...

    journal_title:International journal of cancer

    pub_type: 临床试验,杂志文章

    doi:

    authors: Staib L,Birebent B,Somasundaram R,Purev E,Braumüller H,Leeser C,Küttner N,Li W,Zhu D,Diao J,Wunner W,Speicher D,Beger HG,Song H,Herlyn D

    更新日期:2001-04-01 00:00:00

  • Inhibition of syngeneic fibrosarcoma growth by lymphocytes sensitized on tumor-cell monolayers in the presence of the thymic humoral factor.

    abstract::The present experiments were performed to investigate the possibility of inhibiting tumor growth in vivo with syngeneic lymphocytes sensitized in vitro on monolayers of the tumor under test, and to study the effect of a thymic humoral factor (THF) in this sensitization process. Monolayers of fibrosarcoma cells were us...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910150612

    authors: Small M,Trainin N

    更新日期:1975-06-15 00:00:00

  • Evaluation of CA 125 as a serum marker of hepatocellular carcinoma.

    abstract::Serum CA 125 concentrations were raised in 90.4% of 115 southern African black patients with hepatocellular carcinoma. Seventy-four percent of 62 patients with amebic hepatic abscess, 60% of 40 patients with chronic hepatic parenchymal disease (chronic hepatitis or cirrhosis), and 60.9% of 41 patients with acute viral...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910460510

    authors: Elias J,Kew MC

    更新日期:1990-11-15 00:00:00

  • Corynebacterium parvum prevents immunization to admixed irradiated tumor cells by a local process.

    abstract::Immunization of mice with 10(6) irradiated LSTRA murine leukemia cells (LX) induced weak immunity to subsequent tumor-cell challenge. Admixture of low doses (1.4-14 micrograms of C. parvum with the LX usually augmented the immunity. Higher doses (1,400-7,000 micrograms) of admixed C. parvum not only failed to augment ...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910290617

    authors: Titus MJ,Bartlett GL,Kreider JW

    更新日期:1982-06-15 00:00:00

  • Deficiency in surface expression of E-selectin ligand promotes lung colonization in a mouse model of breast cancer.

    abstract::Expression of sialyl Lewis(x) (sLe(x)) and sLe(a) on tumor cells is thought to facilitate metastasis by promoting cell adhesion to selectins on vascular endothelial cells. Experiments supporting this concept usually bypass the early steps of the metastatic process by employing tumor cells that are injected directly in...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.21192

    authors: Monzavi-Karbassi B,Whitehead TL,Jousheghany F,Artaud C,Hennings L,Shaaf S,Slaughter A,Korourian S,Kelly T,Blaszczyk-Thurin M,Kieber-Emmons T

    更新日期:2005-11-10 00:00:00

  • Genetic variants in one-carbon metabolism genes and breast cancer risk in European American and African American women.

    abstract::Folate-mediated one-carbon metabolism plays critical roles in DNA synthesis, repair and DNA methylation. The impact of single nucleotide polymorphisms (SNPs) in folate-metabolizing enzymes has been investigated in risk of breast cancer among European or Asian populations, but not among women of African ancestry. We co...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.29434

    authors: Gong Z,Yao S,Zirpoli G,David Cheng TY,Roberts M,Khoury T,Ciupak G,Davis W,Pawlish K,Jandorf L,Bovbjerg DH,Bandera EV,Ambrosone CB

    更新日期:2015-08-01 00:00:00

  • Erionite and asbestos differently cause transformation of human mesothelial cells.

    abstract::Malignant mesothelioma (MM) is an aggressive tumor associated with environmental or occupational exposure to asbestos fibers. Erionite is a fibrous zeolite, morphologically similar to asbestos and it is assumed to be even more carcinogenic. Onset and progression of MM has been suggested as the result of the cooperatio...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.22687

    authors: Bertino P,Marconi A,Palumbo L,Bruni BM,Barbone D,Germano S,Dogan AU,Tassi GF,Porta C,Mutti L,Gaudino G

    更新日期:2007-07-01 00:00:00

  • Metallothionein gene expression and resistance to cisplatin in human ovarian cancer.

    abstract::Intracellular thiols have been proposed as mediators of resistance to alkylating agents and cisplatin. As metallothionein is the predominant protein thiol, we examined its relationship to cisplatin resistance in human ovarian cancer cell lines. A human ovarian carcinoma cell line, A2780, derived from an untreated pati...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910450306

    authors: Schilder RJ,Hall L,Monks A,Handel LM,Fornace AJ Jr,Ozols RF,Fojo AT,Hamilton TC

    更新日期:1990-03-15 00:00:00

  • Treatment of oral leukoplakia with a low-dose of beta-carotene and vitamin C supplements: a randomized controlled trial.

    abstract::Management of oral leukoplakia-a potentially malignant disorder-is currently not evidence-based. Of the few randomized trials that have been reported, most have negative data. Therefore, a multi-centre, randomized, double-blind controlled trial (RCT) was undertaken to evaluate the use of low-dose beta-carotene combine...

    journal_title:International journal of cancer

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1002/ijc.29156

    authors: Nagao T,Warnakulasuriya S,Nakamura T,Kato S,Yamamoto K,Fukano H,Suzuki K,Shimozato K,Hashimoto S

    更新日期:2015-04-01 00:00:00

  • Physical activity and risk for breast cancer a prospective cohort study among Swedish twins.

    abstract::The epidemiologic association between physical activity and breast cancer has been corroborated in many studies. Some inconsistencies remain, possibly due to variation in life periods for exposure assessment, confounding and undetected effect modification. In our cohort study, we address some of these questions by tak...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.10447

    authors: Moradi T,Adami HO,Ekbom A,Wedrén S,Terry P,Floderus B,Lichtenstein P

    更新日期:2002-07-01 00:00:00

  • Cancer risk among patients with condylomata acuminata.

    abstract::Condylomata acuminata have been shown to increase the risk of anogenital cancers. However, previous studies have been of limited sample size and/or short follow-up duration, which prevent precise estimates of long-term excess risk, especially for specific cancer sites. We estimated the risk of specific cancers in a la...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.21892

    authors: Nordenvall C,Chang ET,Adami HO,Ye W

    更新日期:2006-08-15 00:00:00

  • Expression of the ALK protein by anaplastic large-cell lymphomas correlates with high proliferative activity.

    abstract::A variable fraction of anaplastic large-cell lymphomas (ALCLs) exhibits a t(2;5)(p23;q35) translocation that results in expression of the chimeric hyperphosphorylated protein NPM-ALK (p80). Tumor cells expressing NPM-ALK exhibit markedly enhanced proliferative activity, but comparative cellular kinetic studies on ALK(...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0215(20000615)86:6<777::aid-ijc

    authors: Leoncini L,Lazzi S,Scano D,Mura A,Onida A,Massarelli G,Tosi P,Barbini P,Cevenini G,Massai MR,Pileri S,Falini B,Giordano A,Kraft R,Laissue JA,Cottier H

    更新日期:2000-06-15 00:00:00

  • A-kinase anchoring protein 3 messenger RNA expression in ovarian cancer and its implication on prognosis.

    abstract::A-kinase anchoring protein 3 (AKAP3) is a sperm protein and its expression appears to be restricted to the testis in normal adult tissues. We investigated AKAP3 mRNA expression in 20 normal ovaries and 54 ovarian cancers of different histological types, grades and stages by reverse transcription-polymerase chain react...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.11565

    authors: Hasegawa K,Ono T,Matsushita H,Shimono M,Noguchi Y,Mizutani Y,Kodama J,Kudo T,Nakayama E

    更新日期:2004-01-01 00:00:00

  • Pigmentary characteristics, sun sensitivity and non-Hodgkin lymphoma.

    abstract::We report on pigmentary characteristics, sun sensitivity and some other possible risk factors for non-Hodgkin lymphoma (NHL) in people 20-74 years of age. A statewide case-control study was conducted in New South Wales, Australia, with population-based sampling of cases (n = 704) and controls (n = 694). Risk of NHL wa...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.20128

    authors: Hughes AM,Armstrong BK,Vajdic CM,Turner J,Grulich A,Fritschi L,Milliken S,Kaldor J,Benke G,Kricker A

    更新日期:2004-06-20 00:00:00

  • Exome sequencing reveals frequent inactivating mutations in ARID1A, ARID1B, ARID2 and ARID4A in microsatellite unstable colorectal cancer.

    abstract::ARID1A has been identified as a novel tumor suppressor gene in ovarian cancer and subsequently in various other tumor types. ARID1A belongs to the ARID domain containing gene family, which comprises of 15 genes involved, for example, in transcriptional regulation, proliferation and chromatin remodeling. In this study,...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.28705

    authors: Cajuso T,Hänninen UA,Kondelin J,Gylfe AE,Tanskanen T,Katainen R,Pitkänen E,Ristolainen H,Kaasinen E,Taipale M,Taipale J,Böhm J,Renkonen-Sinisalo L,Mecklin JP,Järvinen H,Tuupanen S,Kilpivaara O,Vahteristo P

    更新日期:2014-08-01 00:00:00

  • Downregulation of SERPINB13 expression in head and neck squamous cell carcinomas associates with poor clinical outcome.

    abstract::Tumorigenesis of head and neck squamous cell carcinomas (HNSCC) is associated with various genetic changes such as loss of heterozygosity (LOH) on human chromosome 18q21. This chromosomal region maps a gene cluster coding for a family of intracellular serine protease inhibitors (serpins), including SERPINB13. As SERPI...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.24507

    authors: de Koning PJ,Bovenschen N,Leusink FK,Broekhuizen R,Quadir R,van Gemert JT,Hordijk GJ,Chang WS,van der Tweel I,Tilanus MG,Kummer JA

    更新日期:2009-10-01 00:00:00

  • A novel high-affinity human monoclonal antibody to mesothelin.

    abstract::Mesothelin is a glycosylphosphatidylinositol-anchored glycoprotein that is highly expressed on the cell surface of mesothelioma, ovarian cancer and other malignant tumors. The interaction between mesothelin and CA125 (also called MUC16) may facilitate the implantation and metastasis of tumors in the peritoneal cavity....

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.25557

    authors: Ho M,Feng M,Fisher RJ,Rader C,Pastan I

    更新日期:2011-05-01 00:00:00

  • Two survivin polymorphisms are cooperatively associated with bladder cancer susceptibility.

    abstract::Abnormal survivin expression has been reported to be involved in many types of cancer. A single-nucleotide polymorphism (SNP), C-31G, located in the promoter region of survivin reportedly may alter the mRNA level, while the significance of the nonsynonymous SNP A9194G in exon 4 has not yet been clarified. Here, the as...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.25850

    authors: Kawata N,Tsuchiya N,Horikawa Y,Inoue T,Tsuruta H,Maita S,Satoh S,Mitobe Y,Narita S,Habuchi T

    更新日期:2011-10-15 00:00:00

  • Farnesyl transferase inhibitor treatment of breast cancer cells leads to altered RhoA and RhoC GTPase activity and induces a dormant phenotype.

    abstract::Farnesyl transferase inhibitors (FTIs) were shown to be effective in modulating tumor growth in Ras-transformed tumor cells. Recent studies have focused on Rho GTPases as putative targets of FTI action. Previously, we demonstrated that FTIs were effective in inhibiting the growth and invasiveness of RhoC GTPase-overex...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.25655

    authors: Chatterjee M,van Golen KL

    更新日期:2011-07-01 00:00:00