Cytotoxic activity of 7-N-(2-((2-(-gamma-L-glutamylamino)- ethyl)dithio)ethyl)-mitomycin C and metabolites in cell lines with different resistance patterns.

Abstract:

:In this study the activity of KW-2149 and two of its metabolites, M-16 and M-18, was measured against cell lines with different types of resistance. The influence of these metabolites and of the exposure time on the cytotoxic efficacy of KW-2149 was investigated. Against the human ovarian carcinoma cell lines, AOvC and A2780, KW-2149 was more active than mitomycin C (MMC), with an IC50 of, respectively, 3.4 nM and 9.82 microM for KW-2149 and 18.2 nM and 67.71 microM for MMC. Activity of M-18 was significant against both cell lines and was comparable with that of KW-2149. Against an MMC-resistant cell line, AOvCMMC, the resistance factor (RF) for KW-2149 was 3.1 versus 8.0 for MMC. Tested against a cisplatin-resistant cell line, AOvCCDDP, KW-2149 had a RF of 7.7 versus 2.4 for MMC. Increasing the exposure time from 1 to 8 h decreased the RF for KW-2149 from 7.7 to 3.0. In an MDR mediated resistant cell line, A2780mdr+, prolongation of exposure time increased RF for KW-2149 and MMC but decreased RF for M-18 from 7.0 at 1 h to 5.3 at 8 h. Tested against a rat colon carcinoma cell line CC531, KW-2149 and M-18 again demonstrated superior or equal activity compared with MMC, IC50 being, respectively, 0.6, 2.1 and 2.6. Here again M-18 showed an aberrant sensitivity pattern, as its activity decreased with mdr-1 expression in contrast to the other mitomycins. Our data confirm the activity of KW-2149 as an agent with equal or superior activity as compared with MMC. It is concluded that the metabolite M-18 can contribute to the activity of KW-2149. Efficacy of both KW-2149 and its metabolites increases with increasing exposure times. The increments of exposure time appeared even as a means to overcome resistance in some instances.

journal_name

Anticancer Drugs

journal_title

Anti-cancer drugs

authors

Dirix LY,Gheuens EE,van der Heyden S,van Oosterom AT,De Bruijn EA

doi

10.1097/00001813-199406000-00013

subject

Has Abstract

pub_date

1994-06-01 00:00:00

pages

343-54

issue

3

eissn

0959-4973

issn

1473-5741

journal_volume

5

pub_type

杂志文章
  • Use of corticosteroids in neuro-oncology.

    abstract::Glucocorticosteroids (GC) play an important role in the treatment of neuro-oncologic patients. GC are used for the management of malignant brain tumors, either primary of secondary, neoplastic epidural spinal cord compression (NESC), as adjuvant chemotherapy of some central nervous system tumors and perioperatively in...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章,评审

    doi:10.1097/00001813-199502000-00002

    authors: Koehler PJ

    更新日期:1995-02-01 00:00:00

  • Evaluations of biomarkers associated with sensitivity to 5-fluorouracil and taxanes for recurrent/advanced breast cancer patients treated with capecitabine-based first-line chemotherapy.

    abstract::The aim of the present study was to investigate the gene expression of biomarkers associated with the sensitivity to fluoropyrimidine and taxanes in recurrent/advanced breast cancer patients treated with first-line capecitabine chemotherapy. We evaluated the clinicopathological/prognostic significance of thymidylate s...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0b013e32834f7ef4

    authors: Zhao HY,Huang H,Hu ZH,Huang Y,Lin SX,Tian Y,Lin TY

    更新日期:2012-06-01 00:00:00

  • S-allylcysteine induces cytotoxic effects in two human lung cancer cell lines via induction of oxidative damage, downregulation of Nrf2 and NF-κB, and apoptosis.

    abstract::In this study, we investigated the putative cytotoxic effect elicited by the garlic-derived compound S-allylcysteine (SAC) in two human cancer cell lines (HCC827 and NCI-H1975) in order to develop an experimental approach to the therapeutic potential of this molecule for lung cancer. Cells were incubated for 24, 48 an...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0000000000001015

    authors: Orozco-Morales M,Hernández-Pedro NY,Barrios-Bernal P,Arrieta O,Ruiz-Godoy LM,Aschner M,Santamaría A,Colín-González AL

    更新日期:2021-02-01 00:00:00

  • Triterpenoids as new promising anticancer drugs.

    abstract::Triterpenoids are structurally diverse organic compounds, characterized by a basic backbone modified in multiple ways, allowing the formation of more than 20 000 naturally occurring triterpenoid varieties. Several triterpenoids, including ursolic and oleanolic acid, betulinic acid, celastrol, pristimerin, lupeol, and ...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章,评审

    doi:10.1097/CAD.0b013e328330fd90

    authors: Petronelli A,Pannitteri G,Testa U

    更新日期:2009-11-01 00:00:00

  • Dihydroartemisinin induces apoptosis in human leukemia cells HL60 via downregulation of transferrin receptor expression.

    abstract::Dihydroartemisinin (DHA), a water-soluble active metabolite of artemisinin derivatives, is the safest and most effective antimalarial analog of artemisinin. In the present investigation, we assessed the apoptotic effect of DHA on leukemia HL60 cells and its regulation of transferrin receptor (TfR). Cell growth inhibit...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/cad.0b013e3282f3f152

    authors: Zhou HJ,Wang Z,Li A

    更新日期:2008-03-01 00:00:00

  • Neoadjuvant TPF in locally advanced head and neck cancer can be followed by radiotherapy combined with cisplatin or cetuximab: a study of 157 patients.

    abstract::Neoadjuvant TPF (docetaxel, cisplatin, 5-fluorouracil), followed by radiotherapy or chemoradiotherapy with weekly carboplatin, increases overall survival and organ preservation. We assessed whether TPF could be used in routine practice and whether radiotherapy potentiated with cisplatin or cetuximab was feasible and c...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章,多中心研究

    doi:10.1097/CAD.0b013e328360b9d6

    authors: Fayette J,Bonnin N,Ferlay C,Lallemant B,Ramade A,Favrel V,Zrounba P,Chabaud S,Pommier P,Poupart M,Céruse P

    更新日期:2013-07-01 00:00:00

  • Effects of Taxotere and taxol on in vitro colony formation of freshly explanted human tumor cells.

    abstract::Taxotere (RP 56976, NSC 628503) is a new semisynthetic analog of taxol (NSC 125973) with promising antitumor activity in a variety of preclinical screening systems. Clinical responses after treatment with taxol have been observed in ovarian cancer, breast, lung cancer and melanoma. Both agents act through induction of...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/00001813-199204000-00008

    authors: Hanauske AR,Degen D,Hilsenbeck SG,Bissery MC,Von Hoff DD

    更新日期:1992-04-01 00:00:00

  • The influence of storage on cytotoxic drug activity in an ATP-based chemosensitivity assay.

    abstract::The use of viability assays to assess the effect of antineoplastic agents on cell lines and tumor cells is an important investigative tool and may have clinical relevance. Such assays require very small quantities of drugs and it is the practice of many laboratories to freeze aliquots of drugs for use in these assays ...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/00001813-199404000-00007

    authors: Hunter EM,Sutherland LA,Cree IA,Subedi AM,Hartmann D,Linder D,Andreotti PE

    更新日期:1994-04-01 00:00:00

  • Population pharmacokinetic approach to compare oral and i.v. administration of etoposide.

    abstract::The antitumor effect of etoposide (ETO) may be related to duration of exposure to a relatively low serum level while myelosuppression may be dependent on peak ETO serum levels. With regard to such therapeutic ranges, duration of exposure to predefined plasma ETO concentration ranges and the related AUC (expressed as p...

    journal_title:Anti-cancer drugs

    pub_type: 临床试验,杂志文章

    doi:10.1097/00001813-199910000-00003

    authors: Würthwein G,Krümpelmann S,Tillmann B,Real E,Schulze-Westhoff P,Jürgens H,Boos J

    更新日期:1999-10-01 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

  • Artesunate induces G0/G1 cell cycle arrest and iron-mediated mitochondrial apoptosis in A431 human epidermoid carcinoma cells.

    abstract::The anticancer effects of artesunate (ART) have been well documented. However, its potential against skin cancer has not been explored yet. Herein we reported that 60 μmol/l ART effectively inhibited A431 (human epidermoid carcinoma cells) growth but not that of HaCaT (normal human keratinocyte cells). Our results rev...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0b013e328350e8ac

    authors: Jiang Z,Chai J,Chuang HH,Li S,Wang T,Cheng Y,Chen W,Zhou D

    更新日期:2012-07-01 00:00:00

  • Nimotuzumab suppresses epithelial-mesenchymal transition and enhances apoptosis in low-dose UV-C treated salivary adenoid cystic carcinoma cell lines in vitro.

    abstract::Salivary adenoid cystic carcinoma (SACC), which is one of the most common malignant tumors of the salivary glands, is associated with a poor long-term outcome. There are currently few therapeutic options for patients with SACC. Recent studies have shown the potential of the application of ultraviolet-C (UV-C) irradiat...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0000000000000139

    authors: Jiang Y,Ge XY,Liu SM,Zheng L,Huang MW,Shi Y,Fu J,Zhang JG,Li SL

    更新日期:2014-10-01 00:00:00

  • Potential anticancer role of colchicine-based derivatives: an overview.

    abstract::Colchicine, the main alkaloid of the poisonous plant meadow saffron (Colchicum autumnale L.), is a classical drug used for the treatment of gout and familial Mediterranean fever. Although colchicine is not clinically used to treat cancer because of toxicity, it exerts antiproliferative effects through the inhibition o...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章,评审

    doi:10.1097/CAD.0000000000000464

    authors: Kumar A,Sharma PR,Mondhe DM

    更新日期:2017-03-01 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

  • Characterization of molecular events in a series of bladder urothelial carcinoma cell lines with progressive resistance to arsenic trioxide.

    abstract::Our previous studies have shown that arsenic trioxide (As2O3), a novel anti-cancer agent, may be active against urothelial carcinomas. A series of bladder urothelial carcinoma cells with progressive As2O3 resistance were established and studied to reveal molecular events in relation to the mechanisms of resistance to ...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/00001813-200409000-00007

    authors: Hour TC,Huang CY,Lin CC,Chen J,Guan JY,Lee JM,Pu YS

    更新日期:2004-09-01 00:00:00

  • Role of NK-1 and NK-2 tachykinin receptor antagonism on the growth of human breast carcinoma cell line MDA-MB-231.

    abstract::We demonstrate that neurokinin A (NKA) and substance P (SP) play a role in the proliferation of the estrogen receptor-negative (ER-) cell line MDA-MB-231, a human breast carcinoma expressing both NK-1 and NK-2 receptors. In vitro experiments showed that the specific receptor antagonists MEN 11,467 (NK-1) and nepadutan...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/00001813-200511000-00007

    authors: Bigioni M,Benzo A,Irrissuto C,Maggi CA,Goso C

    更新日期:2005-11-01 00:00:00

  • A small randomized phase III single-center trial on postoperative UFT administration in patients with completely resected non-small cell lung cancer.

    abstract::Our objective was to clarify the efficacy of UFT administration after the complete resection of non-small cell lung cancer (NSCLC) at a single-center institution, avoiding the biases produced by interinstitutional differences. A total of 30 patients who underwent the complete resection of NSCLC at our hospital between...

    journal_title:Anti-cancer drugs

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1097/00001813-200401000-00005

    authors: Ueda H,Sakada T,Kuwahara M,Motohiro A

    更新日期:2004-01-01 00:00:00

  • Overall prognostic impact of C-reactive protein level in patients with metastatic renal cell carcinoma treated with sorafenib.

    abstract::C-reactive protein (CRP) is an independent prognostic factor for renal cell carcinoma (RCC). The aim of the present study was to investigate the overall prognostic impact of CRP in patients with metastatic RCC treated with sorafenib. Between April 2008 and December 2014, 40 consecutive patients with metastatic RCC wer...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0000000000000417

    authors: Fujita T,Nishi M,Tabata K,Matsumoto K,Yoshida K,Iwamura M

    更新日期:2016-11-01 00:00:00

  • MLH1-deficient tumor cells are resistant to lipoplatin, but retain sensitivity to lipoxal.

    abstract::Lipoplatin, currently under phase III evaluation, is a novel liposomal cisplatin formulation highly effective against cancers. Lipoplatin has eliminated or reduced the systemic toxicity frequently seen for cisplatin. The objective of the present study was to determine whether the cytotoxic effect of lipoplatin is depe...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/00001813-200603000-00010

    authors: Fedier A,Poyet C,Perucchini D,Boulikas T,Fink D

    更新日期:2006-03-01 00:00:00

  • Phase II study of miltefosine 6% solution as topical treatment of skin metastases in breast cancer patients.

    abstract::Topical treatment of skin metastases with a cytotoxic agent is attractive for its easy self-administration and absence of major systemic interference. Miltefosine exerts its cytotoxicity by acting on cell membrane phospholipids and can be administered topically. Twenty breast cancer patients with progression of skin m...

    journal_title:Anti-cancer drugs

    pub_type: 临床试验,杂志文章

    doi:10.1097/00001813-200011000-00006

    authors: Smorenburg CH,Seynaeve C,Bontenbal M,Planting AS,Sindermann H,Verweij J

    更新日期:2000-11-01 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

  • Antitumor activity, optimum administration method and pharmacokinetics of 13,14-dihydro-15-deoxy-deoxy-Delta7 -prostaglandin A1 methyl ester (TEI-9826) integrated in lipid microspheres (Lipo TEI-9826).

    abstract::13,14-Dihydro-15-deoxy-Delta7-prostaglandin A1 methyl ester (TEI-9826), an antitumor prostaglandin analog, is a candidate for clinical trial. In the present study, we examined its biological stability in vitro, antitumor activity in vitro and in vivo, and pharmacokinetics. Although TEI-9826 was rapidly hydrolyzed to t...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/00001813-200103000-00008

    authors: Fukushima S,Takeuchi Y,Kishimoto S,Yamashita S,Uetsuki K,Shirakawa S,Suzuki M,Furuta K,Noyori R,Sasaki H,Kikuchi Y,Kita T,Yamori T,Sawada J,Kojima M,Hazato A,Kurozumi S,Fukushima M

    更新日期:2001-03-01 00:00:00

  • Antiproliferative effects of interleukin-12 treatment on human tumor colony-forming units taken directly from patients.

    abstract::Interleukin-12 (IL-12) has important immunomodulatory effects on T and natural killer (NK) cells that might be exploited in anticancer treatment. Murine IL-12 models have shown antimetastatic and antitumor effects against murine tumors in vivo. Data on the effects of human IL-12 on human tumors are confined to 51Cr-re...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/00001813-199605000-00006

    authors: Izquierdo MA,Degen D,Sypek JP,Von Hoff DD

    更新日期:1996-05-01 00:00:00

  • Dihydroartemisinin inhibits growth of pancreatic cancer cells in vitro and in vivo.

    abstract::Dihydroartemisinin (DHA), a semisynthetic derivative of artemisinin, has recently shown antitumor activity in various cancer cells. Its effect on pancreatic cancer is, however, unknown and the mechanism is unclear. The study aims to investigate its antitumor activity and underlying mechanisms in human pancreatic cance...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0b013e3283212ade

    authors: Chen H,Sun B,Pan S,Jiang H,Sun X

    更新日期:2009-02-01 00:00:00

  • Galactosylated gelatin nanovectors of doxorubicin inhibit cell proliferation and induce apoptosis in hepatocarcinoma cells.

    abstract::We have synthesized and characterized doxorubicin (DOX)-loaded galactosylated gelatin nanovectors using in vitro and in vivo for targeting liver cells including hepatocarcinoma cells. Galactosylated and nongalactosylated gelatin nanovectors (GL-GN-DOX and GN-DOX) were spherical in shape and had mean sizes of about 95....

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0b013e328351424f

    authors: Garg M,Madan J,Pandey RS,Sardana S,Katyal A,Chandra R

    更新日期:2012-09-01 00:00:00

  • Asbestos-related benign disease and cancer: symptoms and treatment.

    abstract::Long lasting occupational exposure to asbestos dust may cause skin corns, benign pleural effusion, hyaline plaques of the parietal pleura, diffuse thickening of the pulmonary pleura, and asbestosis, i.e. diffuse interstitial pulmonary fibrosis. Malignant disorders include lung cancer and mesothelioma of the pleura, pe...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章,评审

    doi:10.1097/00001813-199012000-00012

    authors: Gruber UF

    更新日期:1990-12-01 00:00:00

  • Pharmacokinetics of hydroxyurea in nude mice.

    abstract::Extrachromosomal DNA is the predominant form of gene amplification in human tumors. Hydroxyurea (HU) concentrations of 100-150 microM have been promising in vitro for extrachromosomal DNA elimination. The study objective was to determine the HU dose-concentration relationship in nude mice with HU doses from 0 to 200 m...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/00001813-199410000-00009

    authors: Van den Berg CL,McGill JR,Kuhn JG,Walsh JT,De La Cruz PS,Davidson KK,Wahl GM,Von Hoff DD

    更新日期:1994-10-01 00:00:00

  • Modification of the sensitivity to cisplatin with c-myc over-expression or down-regulation in colon cancer cells.

    abstract::Human colon cancer SW480 cells express the c-myc gene. On the other hand, SW480DDP cell lines resistant to cisplatin exhibited decreased c-myc gene expression, but their cell growth rates remained similar to those of their parental cells. Antisense oligonucleotides to c-myc inhibited c-myc expression and induced incre...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/00001813-200111000-00006

    authors: Funato T,Kozawa K,Kaku M,Sasaki T

    更新日期:2001-11-01 00:00:00

  • Bendamustine hydrochloride activity against doxorubicin-resistant human breast carcinoma cell lines.

    abstract::The cytotoxic activity of bendamustine hydrochloride was evaluated against human ovarian and breast carcinoma cell lines including cell lines resistant to cisplatin and doxorubicin in vitro. The relative degree of resistance to bendamustine hydrochloride was lower in all cell lines compared with cyclophosphamide, melp...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/00001813-199606000-00007

    authors: Strumberg D,Harstrick A,Doll K,Hoffmann B,Seeber S

    更新日期:1996-06-01 00:00:00

  • Targeted therapy for lung cancer.

    abstract::Lung cancer is considered the number one killer among all cancers. Recent observations have altered the treatment paradigm for non-small-cell lung cancer (NSCLC). The discovery of activating mutations in the epidermal growth factor receptor and anaplastic lymphoma kinase positivity has made personalized treatment for ...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章,评审

    doi:10.1097/CAD.0b013e3283585149

    authors: Petrosyan F,Daw H,Haddad A,Spiro T

    更新日期:2012-11-01 00:00:00