Camptothecin analogs with enhanced activity against human breast cancer cells. I. Correlation of potency with lipophilicity and persistence in the cleavage complex.

Abstract:

:The effect of 7-alkyl substitutions on growth inhibition in seven Camptothecin (CPT) ring systems with various groups at the ten position was evaluated in three human breast cancer cell lines that model (1) hormone-sensitive (MCF-7/wt), (2) hormone insensitive (MDA-MB-231), or (3) alkylator-resistant (MCF-7/4-hc) forms of disease. To assess the impact of persistence of cleavage complexes on antiproliferative activity, a post-exposure recovery period in drug-free medium was incorporated into the growth inhibition assay. This modification produced on average a twofold reduction in the growth inhibition endpoint (the IC50), suggesting a greater apoptotic response. The results further revealed a three log range in potency from a mean IC50 of 2 nM (7-butyl-10,11-methylenedioxy-CPT) to 2.5 microM (7-bromomethyl-10-hydryoxy-CPT). Increasing 7-alkyl chain length in six of the ten-substituted CPTs enhanced potency, which was directly correlated with persistence of topoisomerase I-induced DNA cleavage complexes in 10-hydroxy, 10-methoxy, and 10,11-methylenedioxy substituted CPTs. Modeling of the binding mode of 7-butyl-10-amino-CPT revealed a direct hydrogen bond contact for the 10-amino to the side chain of Glu-356 of Core Subdomain I of top1 in addition to known contacts found for other camptothecins. More important, residues 350-356 and 425-431 of Core Subdomain I may provide induced fit stabilization to the lipophilic alkyl moiety at the seven position.

authors

Adams DJ,da Silva MW,Flowers JL,Kohlhagen G,Pommier Y,Colvin OM,Manikumar G,Wani MC

doi

10.1007/s00280-005-0007-6

keywords:

subject

Has Abstract

pub_date

2006-01-01 00:00:00

pages

135-44

issue

2

eissn

0344-5704

issn

1432-0843

journal_volume

57

pub_type

杂志文章
  • Clinical and in vitro studies of the correlation between MGMT and the effect of streptozocin in pancreatic NET.

    abstract:PURPOSE:This study aimed to determine the correlation between DNA repair enzyme O6-methylguanine DNA methyltransferase (MGMT) status and the response to streptozocin in advanced well-differentiated pancreatic neuroendocrine tumors (WD panNETs). METHODS:To test the hypothesis that MGMT deficiency was required for an al...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-018-3700-y

    authors: Hijioka S,Sakuma K,Aoki M,Mizuno N,Kuwahara T,Okuno N,Hara K,Yatabe Y

    更新日期:2019-01-01 00:00:00

  • Safety of topotecan monotherapy for relapsed small cell lung cancer patients with pre-existing interstitial lung disease.

    abstract:PURPOSE:To investigate the safety of intravenous topotecan monotherapy for relapsed small cell lung cancer (SCLC) patients with pre-existing interstitial lung disease (ILD). METHODS:A total of 77 patients who received topotecan for the treatment of relapsed SCLC between April 2007 and April 2014 were reviewed. Patient...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-015-2816-6

    authors: Enomoto Y,Inui N,Imokawa S,Karayama M,Hasegawa H,Ozawa Y,Matsui T,Yokomura K,Suda T

    更新日期:2015-09-01 00:00:00

  • Autophagy, a novel target for chemotherapeutic intervention of thyroid cancer.

    abstract:PURPOSE:Thyroid cancers with unsatisfactory curative effect nowadays are the most common malignant tumors of the endocrine system. Apoptosis evasion, a hallmark of cancer, has driven the search of stimulating novel cell death way in cancer therapy. This review aims to explore the relationship between autophagy and thyr...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,评审

    doi:10.1007/s00280-013-2363-y

    authors: Li LC,Liu GD,Zhang XJ,Li YB

    更新日期:2014-03-01 00:00:00

  • Oleandrin synergizes with cisplatin in human osteosarcoma cells by enhancing cell apoptosis through activation of the p38 MAPK signaling pathway.

    abstract:PURPOSE:Our previous studies have reported the antitumor effect of oleandrin on osteosarcoma; however, its chemosensitizing effect in osteosarcoma treatment is still unknown. Therefore, we explored the sensitizing effects of oleandrin to cisplatin in osteosarcoma and investigated the potential mechanisms. METHODS:Afte...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-018-3692-7

    authors: Yong L,Ma Y,Zhu B,Liu X,Wang P,Liang C,He G,Zhao Z,Liu Z,Liu X

    更新日期:2018-12-01 00:00:00

  • MDA-MB-435 cells are from melanoma, not from breast cancer.

    abstract::For years, MDA-MB-435 cells have been widely but erroneously used as breast cancer cells with aggressive behaviour. Recent data show that they are in fact melanoma cells. However, many scientists are still unaware of this "new" identity. ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 评论,信件

    doi:10.1007/s00280-008-0776-9

    authors: Lacroix M

    更新日期:2009-02-01 00:00:00

  • Disulfiram: a novel repurposed drug for cancer therapy.

    abstract::Cancer is a major health issue worldwide and the global burden of cancer is expected to reduce the costs of treatment as well as prolong the survival time. One of the promising approaches is drug repurposing, because it reduces costs and shortens the production cycle of research and development. Disulfiram (DSF), whic...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,评审

    doi:10.1007/s00280-020-04216-8

    authors: Lu C,Li X,Ren Y,Zhang X

    更新日期:2021-01-10 00:00:00

  • Cytotoxicity of ketoconazole in malignant cell lines.

    abstract::The cytotoxic effects of ketoconazole, an antifungal agent known to have some activity against human prostate cancer, adrenal cancer, and male metastatic breast cancer, were evaluated using colony-growth and clonogenic assays in eight malignant cell lines. The cytotoxicity of ketoconazole showed a dose- and time-depen...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00264198

    authors: Rochlitz CF,Damon LE,Russi MB,Geddes A,Cadman EC

    更新日期:1988-01-01 00:00:00

  • Evodiamine inhibits the migration and invasion of nasopharyngeal carcinoma cells in vitro via repressing MMP-2 expression.

    abstract:PURPOSE:Evodiamine is one of active alkaloids isolated from the traditional Chinese medicine Evodia rutaecarpa Bentham and has various pharmacological properties. In this study, we investigated its effects on the migration, invasion, and associated mechanism in human nasopharyngeal carcinoma (NPC) cells. METHODS:Cell ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-015-2902-9

    authors: Peng X,Zhang Q,Zeng Y,Li J,Wang L,Ai P

    更新日期:2015-12-01 00:00:00

  • Efficacy of infusional 5-fluorouracil, doxorubicin, and mitomycin-C (iFAM) in the treatment of patients with gemcitabine-pretreated pancreatic cancer and analysis of prognostic factors in a salvage setting.

    abstract:PURPOSE:In gemcitabine-pretreated pancreatic cancer, salvage chemotherapy has not been established, and the prognostic factors are not completely known. The purpose of this study was to determine the efficacy and safety of infusional 5-fluorouracil (5-FU), doxorubicin, and mitomycin-C (iFAM) in patients with gemcitabin...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1007/s00280-011-1584-1

    authors: Lim KH,Kim TY,Lee KH,Han SW,Oh DY,Im SA,Kim TY,Bang YJ

    更新日期:2011-10-01 00:00:00

  • Thiolo-, thiono- and dithiocarbonate and thiocarbamate derivatives of demethylpenclomedine as novel anticancer agents.

    abstract:PURPOSE:The purpose of this investigation was to synthesize a series of thiolo-, thiono- and dithiocarbonate and thiocarbamate derivatives of 4-demethylpenclomedine (DM-PEN), the major plasma metabolite of penclomedine (PEN) in patients observed subsequently to be an active antitumor agent and non-neurotoxic in a rat m...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-005-0031-6

    authors: Struck RF,Waud WR

    更新日期:2006-01-01 00:00:00

  • Metronomics chemotherapy: time for computational decision support.

    abstract::Over the last decade, metronomic chemotherapy has been increasingly considered as an attractive strategy for treating cancer in a variety of settings. Beside pharmaco-economic considerations making metronomics a unique opportunity in low- or middle-income countries, revisiting dosing schedules using continuous low dos...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,评审

    doi:10.1007/s00280-014-2546-1

    authors: Barbolosi D,Ciccolini J,Meille C,Elharrar X,Faivre C,Lacarelle B,André N,Barlesi F

    更新日期:2014-09-01 00:00:00

  • Phase II, open-label trial to assess QTcF effects, pharmacokinetics and antitumor activity of afatinib in patients with relapsed or refractory solid tumors.

    abstract:PURPOSE:Afatinib is an irreversible ErbB family blocker currently under evaluation in late-stage clinical trials. This study primarily assessed the cardiac safety, pharmacokinetics and antitumor activity of afatinib in cancer patients. METHODS:In this multicenter, Phase II, open-label, single-arm trial, 60 patients wi...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,多中心研究

    doi:10.1007/s00280-013-2286-7

    authors: Molife LR,Rudman SM,Alam S,Tan DS,Kristeleit H,Middleton G,Propper D,Bent L,Stopfer P,Uttenreuther-Fischer M,Wallenstein G,de Bono J,Spicer J

    更新日期:2013-12-01 00:00:00

  • Serum microRNA-21 predicted treatment outcome and survival in HER2-positive breast cancer patients receiving neoadjuvant chemotherapy combined with trastuzumab.

    abstract:PURPOSE:The purpose of this study was to evaluate the expression of ser-miRNAs at different periods during treatment and analyze their relationship with therapeutic response and prognosis in HER2-positive breast cancer patients receiving neoadjuvant chemotherapy combined with trastuzumab (NCCT). METHODS:Venous blood w...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-019-03937-9

    authors: Liu B,Su F,Lv X,Zhang W,Shang X,Zhang Y,Zhang J

    更新日期:2019-11-01 00:00:00

  • Exposure-response relationship of olaratumab for survival outcomes and safety when combined with doxorubicin in patients with soft tissue sarcoma.

    abstract:PURPOSE:Olaratumab is a recombinant human IgG1 monoclonal antibody against PGDFRα. Olaratumab plus doxorubicin improved survivalversus doxorubicin in an open-label, randomised phase 2 soft tissue sarcoma (STS) trial. We characterised the olaratumab exposure-response relationship for progression-free survival (PFS), ove...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1007/s00280-018-3723-4

    authors: Jones RL,Mo G,Baldwin JR,Peterson PM,Ilaria RL Jr,Conti I,Cronier DM,Tap WD

    更新日期:2019-01-01 00:00:00

  • A phase I study of HER1, HER2 dual kinase inhibitor lapatinib plus the proteasome inhibitor bortezomib in patients with advanced malignancies.

    abstract:PURPOSE:This phase I trial evaluated the maximum tolerated dose, safety and preliminary efficacy of lapatinib, a HER1, HER2 dual kinase inhibitor plus bortezomib, a proteasome inhibitor, in adult patients with advanced malignancies. METHODS:Patients were enrolled in a standard 3 + 3 design with lapatinib (L) 750, 1000...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-019-03947-7

    authors: Lynce F,Wang H,Petricoin EF,Pohlmann PR,Smaglo B,Hwang J,He AR,Subramaniam DS,Deeken J,Marshall J,Pishvaian MJ

    更新日期:2019-11-01 00:00:00

  • Intravenous paclitaxel against metastasis of human gastric tumors of diffuse type.

    abstract:PURPOSE:Gastric cancer is one of the leading cancerous diseases worldwide. It is diagnosed often at the advanced stage for which chemotherapy is the main treatment option. The prognosis remains poor for metastatic, especially the diffuse type, gastric cancers. We investigated the efficacy of intravenously administered ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-009-1222-3

    authors: Tuan TF,Tsai ML,Yeh KC,Huang HC,Chung CT,Huang CL,Han CH,Chen CP,Wang MH,Shen CC,Lai YK,Lee WS,Hwang LL,Chen CT

    更新日期:2010-09-01 00:00:00

  • Conditions favoring long-term survival after hepatectomy for hepatocellular carcinomas.

    abstract::The present study was aimed at answering the question of what patients with hepatocellular carcinomas could obtain long-term benefits from resectional therapy. The 239 patients hepatectomized from 1973 through 1986, with 33 tumor-free, 3-year survivors, were the subjects of the study. The following criteria for long-t...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00647247

    authors: Yamanaka N,Okamoto E

    更新日期:1989-01-01 00:00:00

  • A phase II study of icotinib and whole-brain radiotherapy in Chinese patients with brain metastases from non-small cell lung cancer.

    abstract:PURPOSE:Icotinib is a new first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. A phase II study was conducted to evaluate the efficacy and safety of icotinib in combination with whole-brain radiotherapy (WBRT) in Chinese NSCLC patients with brain metastases (BMs); the cerebrospinal fluid...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-015-2760-5

    authors: Fan Y,Huang Z,Fang L,Miao L,Gong L,Yu H,Yang H,Lei T,Mao W

    更新日期:2015-09-01 00:00:00

  • Cyclophosphamide and dimethylsulfoxide in the treatment of squamous carcinoma of the lung. Therapeutic efficacy, toxicity, and pharmacokinetics.

    abstract::To determine whether dimethylsulfoxide (DMSO) can potentiate antitumor activity of cyclophosphamide (CYC) in patients with squamous cell carcinoma of the lung, 14 patients were treated with 5 l of a 5% or 6% DMSO solution PO over 3 days and 1,500 mg CYC/m2 IV as a 60-min infusion on the third day of treatment. Serial ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00262327

    authors: Fuks JZ,Egorin MJ,Aisner J,Ostrow SS,Klein ME,Bachur NR,Colvin M,Wiernik PH

    更新日期:1981-01-01 00:00:00

  • Phase I study of the cisplatin analogue 1,1-diamminomethylcyclohexane sulfatoplatinum (TNO-6) (NSC 311056).

    abstract::The cisplatin derivative TNO-6 was evaluated for clinical toxicity in a phase I trial. TNO-6 was given daily for 5 days every 3 weeks as a 30-min IV infusion without hydration. In all, 39 patients with advanced cancer were treated at doses of 2.5-9.0 mg/m2. No dose-limiting nephrotoxicity occurred, but evidence of mil...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00257516

    authors: Sørensen JB,Groth S,Hansen SW,Nissen MH,Rørth M,Hansen HH

    更新日期:1985-01-01 00:00:00

  • Induction of remission in acute promyelocytic leukemia with mitoxantrone.

    abstract::Two patients with acute promyelocytic leukemia in first relapse received mitoxantrone 12 mg/m2/day for 5 days. Both patients received IV heparin with replacement of platelets and coagulation factors for control of disseminated intravascular coagulopathy. Both have achieved a complete remission after one course of trea...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00552732

    authors: Mittelman A,Rieber E,Friedland ML,Arlin ZA

    更新日期:1985-01-01 00:00:00

  • Pingyangmycin downregulates the expression of EGFR and enhances the effects of cetuximab on esophageal cancer cells and the xenograft in athymic mice.

    abstract:PURPOSE:As reported, epidermal growth factor receptor (EGFR) is over expressed in a variety of cancers including esophageal squamous cell carcinoma. Therefore, it becomes one of the potential targets for treating esophageal cancer. Pingyangmycin (PYM), a single A5 component of bleomycin, is currently used for the treat...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-012-1827-9

    authors: Gong JH,Liu XJ,Li Y,Zhen YS

    更新日期:2012-05-01 00:00:00

  • Etoposide: current status and future perspectives in the management of malignant neoplasms.

    abstract::Etoposide has demonstrated highly significant clinical activity against a wide variety of neoplasms, including germ-cell malignancies, small-cell lung cancer, non-Hodgkin's lymphomas, leukemias, Kaposi's sarcoma, neuroblastoma, and soft-tissue sarcomas. It is also one of the important agents in the preparatory regimen...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,评审

    doi:10.1007/BF00684875

    authors: Belani CP,Doyle LA,Aisner J

    更新日期:1994-01-01 00:00:00

  • Tailored preoperative treatment of locally advanced triple negative (hormone receptor negative and HER2 negative) breast cancer with epirubicin, cisplatin, and infusional fluorouracil followed by weekly paclitaxel.

    abstract:BACKGROUND:No specific treatment guidelines are available for triple-negative breast cancers, defined by a lack of expression of estrogen (ER), progesterone (PgR), and HER2 receptors. PATIENTS AND METHODS:We investigated in patients with T2-T3 N0-3 ER, PgR <10% and HER2 negative breast cancers the activity both in ter...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1007/s00280-007-0652-z

    authors: Torrisi R,Balduzzi A,Ghisini R,Rocca A,Bottiglieri L,Giovanardi F,Veronesi P,Luini A,Orlando L,Viale G,Goldhirsch A,Colleoni M

    更新日期:2008-09-01 00:00:00

  • Treatment of resistant metastatic melanoma using sequential epigenetic therapy (decitabine and panobinostat) combined with chemotherapy (temozolomide).

    abstract:PURPOSE:To explore the safety and tolerability of combining two epigenetic drugs: decitabine (a DNA methyltransferase inhibitor) and panobinostat (a histone deacetylase inhibitor), with chemotherapy with temozolomide (an alkylating agent). The purpose of such combination is to evaluate the use of epigenetic priming to ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-014-2501-1

    authors: Xia C,Leon-Ferre R,Laux D,Deutsch J,Smith BJ,Frees M,Milhem M

    更新日期:2014-10-01 00:00:00

  • Phase I dosage finding and pharmacokinetic study of intravenous topotecan and oral erlotinib in adults with refractory solid tumors.

    abstract:PURPOSE:Topotecan is widely used for refractory solid tumors but multi-drug resistance may occur due to tumor expression of ATP-binding cassette (ABC) transporters. Since erlotinib, an inhibitor of the epidermal growth factor receptor, also inhibits several ABC transporters, we performed a phase I study to evaluate the...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-014-2385-0

    authors: Stewart CF,Tagen M,Schwartzberg LS,Blakely LJ,Tauer KW,Smiley LM

    更新日期:2014-03-01 00:00:00

  • 5-Fluorouracil's cytotoxicity is enhanced both in vitro and in vivo by concomitant treatment with hyperthermia and dipyridamole.

    abstract::We obtained evidence that the cytotoxic effect of 5-fluorouracil (5-FU) is augmented when the drug is given in combination with hyperthermia (HYP) and dipyridamole (DP). Nontoxic levels of DP enhanced the combined cytotoxicity of 5-FU and HYP against B16 melanoma and human tumor cells in vitro as measured by the succi...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00685941

    authors: Maehara Y,Sakaguchi Y,Takahashi I,Yoshida M,Kusumoto H,Masuda H,Sugimachi K

    更新日期:1992-01-01 00:00:00

  • Evaluation of p-F-Phe-m-bis-(2-chloroethyl)amino-L-Phe-Met-ethoxy HCl against transplantable and spontaneous murine neoplasia.

    abstract::The therapeutic efficacy of PTT.119, p-F-Phe-m-bis-(2-chloroethyl)amino-L-Phe-Met-ethoxy HCl, was evaluated using the transplantable L1210 leukemia and Ridgway osteogenic sarcoma tumor lines and the spontaneous C3H/StRos mammary tumor and AKR leukemia tumor models. Given in a single i.p. dose at 5-10 mg/kg on day 2 or...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF02897202

    authors: Yagi MJ,Bekesi JG

    更新日期:1990-01-01 00:00:00

  • Granulocyte colony-stimulating factor-induced mobilization of peripheral blood stem cells for autologous and allogeneic transplantation. Fukuoka Bone Marrow Transplantation Group.

    abstract::Peripheral blood stem and progenitor cells (PBSC and PBPC), which circulate at very low levels during steady-state hematopoiesis, show a transient but marked increase during hematologic recovery from marrow-suppressive chemotherapy. To ensure rapid and sustained hematologic engraftment after autologous PBSC transplant...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s002800051051

    authors: Harada M,Teshima T,Fujisaki T,Mizuno S,Miyamoto T,Takamatsu Y,Kubota A,Ohno Y,Kuroiwa M,Takenaka K,Eto T,Akashi K,Gondo H,Okamura T,Inaba S,Niho Y

    更新日期:1996-01-01 00:00:00

  • Potentiation of the antitumour effect of cyclophosphamide in mice by thalidomide.

    abstract:PURPOSE:Thalidomide has recently shown significant promise in the treatment of some types of cancer, and trials in combination with conventional chemotherapy are being undertaken. We wished to determine whether thalidomide potentiated the effect of cyclophosphamide, a commonly used cytotoxic drug, in a murine tumour mo...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-002-0482-y

    authors: Ding Q,Kestell P,Baguley BC,Palmer BD,Paxton JW,Muller G,Ching LM

    更新日期:2002-09-01 00:00:00