Cytotoxicity of cantharidin analogues targeting protein phosphatase 2A.

Abstract:

:Cantharidin is a natural toxin that possesses potent anti-tumor properties. Its clinical application, however, is limited due to severe side-effects. Its cytotoxicity is believed to be mediated by the inhibition of serine/threonine protein phosphatase 2A. In order to identify new compounds with potential clinical therapeutic use, a series of cantharidin analogues, including those with skeletal modifications at 1-C position (analogues 1-6) and those with anhydride modifications (analogues 7-13), were synthesized, and tested for their inhibitory effects on protein phosphatase 2A and their cytotoxicity to a panel of cancer cell lines. In addition, the mode of inhibition of cantharidin and analogue 13 on protein phosphatase 2A was determined by enzymatic kinetics assay. The data indicated that analogue 13 exhibited potent cytotoxicity to all cancer cell lines, and analogues 9, 11 and 12 showed relatively weak cytotoxicity to one or more cell lines, while other analogues showed little cytotoxicity. Accordingly, analogue 13 exhibited potent inhibitory activity on protein phosphatase 2A, and analogues 9, 11 and 12 showed weak inhibitory activity, while other analogues did not show any inhibitory activity. The findings indicate that the cytotoxicity of synthetic cantharidin analogues is likely to be associated with their protein phosphatase 2A inhibitory activity. The mode of inhibition of cantharidin and analogue 13 on protein phosphatase 2A is identified as noncompetitive inhibition by the Lineweaver-Burk plot.

journal_name

Anticancer Drugs

journal_title

Anti-cancer drugs

authors

Shan HB,Cai YC,Liu Y,Zeng WN,Chen HX,Fan BT,Liu XH,Xu ZL,Wang B,Xian LJ

doi

10.1097/01.cad.0000217428.90325.35

subject

Has Abstract

pub_date

2006-09-01 00:00:00

pages

905-11

issue

8

eissn

0959-4973

issn

1473-5741

pii

00001813-200609000-00004

journal_volume

17

pub_type

杂志文章
  • Induction chemotherapy in head and neck cancer: a new paradigm.

    abstract::Five hundred and fifty thousand new head and neck cancer cases are diagnosed each year worldwide. They are mostly locally advanced squamous cell carcinoma with a poor prognosis in terms of locoregional and distant failure. A major challenge for patients with locally advanced squamous cell carcinoma is to achieve a hig...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章,评审

    doi:10.1097/CAD.0b013e3283425871

    authors: Pointreau Y,Atean I,Fayette J,Calais G,Lefebvre JL

    更新日期:2011-08-01 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

  • Determination of the maximal carcinoma/normal skin ratio after HpD or m-THPC administration in Hairless mice (SKH-1) by fluorescence spectroscopy.

    abstract::The two major steps in our study on the treatment of skin carcinomas by photochemotherapy (PCT) were the development of a skin tumor model in Hairless mice by a chemical carcinogenesis and the use of fluorescence spectroscopy, a semi-quantitative and non-invasive method, in order to determine the time after i.p. injec...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/00001813-200002000-00004

    authors: Bossu E,Padilla-Ybarra JJ,Notter D,Vigneron C,Guillemin F

    更新日期:2000-02-01 00:00:00

  • Antitumor effect and tumor level of 5-fluoro-2'-deoxyuridylate following oral administration of tetradecyl 2'-deoxy-5-fluoro-5'-uridylate.

    abstract::The antitumor effect and tumor levels of 5-fluoro-2'-deoxyuridylate (FdUMP) following oral administration of tetradecyl 2'-deoxy-5-fluoro-5'-uridylate (TT-62) were compared with those attained following intravenous (i.v.) or intraperitoneal (i.p.) administration of 5-fluorouracil (5-FU) or 5-fluoro-2'-deoxyuridine (FU...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/00001813-199206000-00013

    authors: Nakajima Y,Iigo M,Hoshi A

    更新日期:1992-06-01 00:00:00

  • Phase II study of paclitaxel in pretreated advanced gastric cancer.

    abstract::Patients with advanced gastric cancer unresponsive or progressing after PELF chemotherapy (5-fluorouracil, leucovorin, cisplatin and epidoxorubicin) received paclitaxel at the dose of 225 mg/m2 every 3 weeks, over 3 h infusion. Thirty-six patients entered the study, and all of them were evaluable for response and toxi...

    journal_title:Anti-cancer drugs

    pub_type: 临床试验,杂志文章

    doi:10.1097/00001813-199804000-00003

    authors: Cascinu S,Graziano F,Cardarelli N,Marcellini M,Giordani P,Menichetti ET,Catalano G

    更新日期:1998-04-01 00:00:00

  • Triterpenoid pristimerin synergizes with taxol to induce cervical cancer cell death through reactive oxygen species-mediated mitochondrial dysfunction.

    abstract::A combined treatment with conventional chemotherapies can enhance the effectiveness of chemotherapeutic agents against cancers. Here, we have shown that the naturally occurring triterpenoids synergistically enhance the response of cervical cancer cells to taxol. Of the triterpenoid compounds, pristimerin enhanced the ...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0b013e328347181a

    authors: Eum DY,Byun JY,Yoon CH,Seo WD,Park KH,Lee JH,Chung HY,An S,Suh Y,Kim MJ,Lee SJ

    更新日期:2011-09-01 00:00:00

  • Thioredoxin reductase and cancer cell growth inhibition by organogold(III) compounds.

    abstract::Thioredoxin (Trx) expression is increased in several human primary cancers associated with aggressive tumor growth and decreased patient survival, and the Trx/Trx reductase (TrxR) system therefore provides an attractive target for cancer drug development. Various gold(III) compounds with none, one, two or three carbon...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/00001813-200606000-00007

    authors: Engman L,McNaughton M,Gajewska M,Kumar S,Birmingham A,Powis G

    更新日期:2006-06-01 00:00:00

  • Evaluation of [131I]iodoerythronitroimidazole as a predictor for the radiosensitizing effect.

    abstract::The aim of this study was to evaluate whether radiolabeled iodoerythronitroimidazole (IETNIM) could predict the radiosensitization effect on tumors. Tumor-bearing mice were irradiated at a dose of 25, 31 and 37 Gy after the injection of IETNIM. They were also exposed to 37 Gy radiation at 35, 70, 140 and 240 min after...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/00001813-199611000-00007

    authors: Inoue T,Yang DJ,Wallace S,Cherif A,Tansey W,Kim EE,Hunter N,Milross CG,Milas L,Podoloff DA

    更新日期:1996-11-01 00:00:00

  • Complete pathologic response with combination oxaliplatin and 5-fluorouracil chemotherapy in an older patient with advanced gastric cancer.

    abstract::Management of gastric cancer in older adults is challenging. Perioperative treatment with epirubicin, cisplatin, and 5-fluorouracil combination chemotherapy and surgery is considered the standard treatment of locally advanced gastric adenocarcinoma. However, this chemotherapy regimen is not well tolerated in older adu...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0b013e32834a2c16

    authors: Amini A,Sanati H

    更新日期:2011-11-01 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

  • Schlafen-11 sensitizes colorectal carcinoma cells to irinotecan.

    abstract::Schlafen-11 (SLFN11) showed a highly significant positive correlation with the response of topoisomerase inhibitors in cancer cell lines derived from prostate, lung, etc. However, this finding has not been validated in colorectal cancers (CRCs). Although irinotecan (CPT-11), a topoisomerase inhibitor, is one of the mo...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0000000000000151

    authors: Tian L,Song S,Liu X,Wang Y,Xu X,Hu Y,Xu J

    更新日期:2014-11-01 00:00:00

  • The immunocytokine L19-TNF eradicates sarcomas in combination with chemotherapy agents or with immune check-point inhibitors.

    abstract::Antibody-cytokine fusion proteins (also called 'immunocytokines') represent an emerging class of biopharmaceutical products, which are being considered for cancer immunotherapy. When used as single agents, pro-inflammatory immunocytokines are rarely capable of inducing complete and durable cancer regression in mouse m...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0000000000000938

    authors: Corbellari R,Nadal L,Villa A,Neri D,De Luca R

    更新日期:2020-09-01 00:00:00

  • Pharmacokinetics and central nervous system toxicity of declopramide (3-chloroprocainamide) in rats and mice.

    abstract::Declopramide (3-chloroprocainamide) has been identified in previous studies as a representative of a new class of chemosensitizers. In this study, the toxicity and pharmacokinetics of declopramide have been investigated and compared with a structural analog, metoclopramide (MCA). Declopramide has not induced central n...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/00001813-199901000-00010

    authors: Hua J,Pero RW,Kane R

    更新日期:1999-01-01 00:00:00

  • Bevacizumab: a safe and effective treatment in a patient with advanced colorectal cancer and repeated removal of metastases.

    abstract::Bevacizumab has been shown to be effective combined with chemotherapy for first-line treatment of advanced colorectal cancer, but little information is available about its efficacy and safety in patients who may be candidates for surgery at any time during the disease. The case history of a female patient with colorec...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/01.cad.0000349778.09614.54

    authors: Castro-Carpeño Jd,Moyano MS,Sáenz EC,Belda-Iniesta C,Batlle JF,Barón MG

    更新日期:2009-04-01 00:00:00

  • [Current treatment of bladder cancer: from epidemiology to surgical treatment].

    abstract::Urothelial carcinoma of the bladder accounts for over 95% of bladder tumours in France. The incidence of this disease is increasing in industrialised countries. Several types of bladder cancer can be distinguished: (1) superficial tumours which have a risk of recurrence and progression, although conservative treatment...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章,评审

    doi:

    authors: Rischmann P

    更新日期:2000-10-01 00:00:00

  • Gene expression changes during the development of estrogen-independent and antiestrogen-resistant growth in breast cancer cell culture models.

    abstract::We have established estrogen-independent and antiestrogen-resistant cell lines from hormone-dependent MCF-7 breast cancer cells by long-term culture in the absence of estrogen, or in the presence of antiestrogen toremifene, respectively. By using a cDNA microarray we compared gene expression profiles among estrogen-in...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0b013e32831845e1

    authors: Pennanen PT,Sarvilinna NS,Ylikomi TJ

    更新日期:2009-01-01 00:00:00

  • Differential regulation of thrombospondin-1 expression and antiangiogenesis of ECV304 cells by trichostatin A and helixor A.

    abstract::Trichostatin A and helixor A increased thrombospondin-1 expression by ECV304 cells at both mRNA and protein levels by transcriptional activation through the enhancement of tsp-1 promoter activity. The induction of thrombospondin-1 by these agents potently reduced ECV 304 cell migration and capillary-like tube formatio...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0b013e3281e4429d

    authors: Hong S,Chang SY,Yeom DH,Kang JH,Hong KJ

    更新日期:2007-10-01 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

  • Tumor cytotoxicity of peritoneal macrophages induced by OK-432.

    abstract::In the present study we investigated the enhancement of cytotoxicity of peritoneal macrophages induced by OK-432. Rats received an i.p. injection of OK-432 at doses of 0.1, 0.5 or 1.0 KE/rat. Two days later, rats were sacrificed and peritoneal macrophages were isolated. Then the number of macrophages was counted, and ...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/00001813-200110000-00010

    authors: Huang Y,Xu Y,Yamagishi H,Hagiwara A

    更新日期:2001-10-01 00:00:00

  • The marine alkaloid naamidine A promotes caspase-dependent apoptosis in tumor cells.

    abstract::Apoptosis is important for normal development and removal of damaged cells. Evasion of apoptosis by cancer cells is one of the key characteristics of many tumor types. Thus, discovering agents that promote apoptosis in tumor cells could have great therapeutic value. Marine natural products have demonstrated great pote...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0b013e32832ae55f

    authors: LaBarbera DV,Modzelewska K,Glazar AI,Gray PD,Kaur M,Liu T,Grossman D,Harper MK,Kuwada SK,Moghal N,Ireland CM

    更新日期:2009-07-01 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

  • Effects of bestatin (Ubenimex) on human T-cell colony formation.

    abstract::The antitumor action of bestatin is considered to be an indirect action mediated by T-cells. Therefore, we investigated the effects of bestatin on the differentiation and proliferation of human precursor T-cells using a colony formation technique. Bestatin did not increase the overall number of T-cell colonies, but it...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/00001813-199102000-00005

    authors: Wakabayashi Y,Hashimoto M,Saitoh K,Osawa H,Koike M,Hirose S

    更新日期:1991-02-01 00:00:00

  • Survival response of a human glioma cell line to hyperthermia associated with rhein.

    abstract::The effect of association of hyperthermia with the anti-inflammatory drug rhein (RH), 4,5-dihydroxyanthraquinone-2-carboxylic acid, on the clonogenic activity of human glioma cells has been examined. RH inhibits neoplastic growth mainly through an ATP depletion, but thermal cell killing is not mediated by the drug-ind...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/00001813-199208000-00015

    authors: Floridi A,Gentile PF,Bruno T,Delpino A,Iacobini C,Benassi M

    更新日期:1992-08-01 00:00:00

  • A prospective randomized controlled trial of tumour chemosensitivity assay directed chemotherapy versus physician's choice in patients with recurrent platinum-resistant ovarian cancer.

    abstract::The primary aim of this randomized trial was to determine response rate and progression-free survival following chemotherapy in patients with platinum-resistant recurrent ovarian cancer, who had been treated according to an ATP-based tumour chemosensitivity assay in comparison with physician's choice. A total of 180 p...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章,随机对照试验

    doi:10.1097/CAD.0b013e3281de727e

    authors: Cree IA,Kurbacher CM,Lamont A,Hindley AC,Love S,TCA Ovarian Cancer Trial Group.

    更新日期:2007-10-01 00:00:00

  • Effect of membrane active 1-alkylpiperidine N-oxides on glycolysis, respiration and ATP level in tumor cells.

    abstract::The aim of this study was to study the effect of the homologous series of 1-alkylpyrrolidine N-oxides on ATP-producing processes in Ehrlich ascites and L1210 murine leukemia cells. 1-Decylpiperidine N-oxide (deP-NO), one of the active compounds, significantly stimulated the course of aerobic glycolysis of Ehrlich cell...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/00001813-199308000-00008

    authors: Miko M,Devinsky F

    更新日期:1993-08-01 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

  • Methotrexate concentrations in cerebrospinal fluid and serum, and the risk of central nervous system relapse in children with acute lymphoblastic leukaemia.

    abstract::The aim of the study was to characterize the relationship between the pharmacokinetics of methotrexate in serum and concentrations in the cerebrospinal fluid, and to analyse the association to risk of a central nervous system relapse in children with acute lymphoblastic leukaemia. In this retrospective study, 353 chil...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0b013e3281430bd1

    authors: Jönsson P,Höglund P,Wiebe T,Schrøder H,Seidel H,Skärby T

    更新日期:2007-09-01 00:00:00

  • Taxol and vinorelbine: a new active combination for disseminated malignant melanoma.

    abstract::We evaluated the activity and toxicity of two sequences of taxol combined with vinorelbine in disseminated malignant melanoma, metastatic beyond regional lymph nodes. Fifteen previously untreated patients, nine males and six females (median age 56 years), were enlisted between May 1994 and February 1995. Eight patient...

    journal_title:Anti-cancer drugs

    pub_type: 临床试验,杂志文章

    doi:10.1097/00001813-199602000-00003

    authors: Retsas S,Mohith A,Mackenzie H

    更新日期:1996-02-01 00:00:00

  • Targeting the type 1 insulin-like growth factor receptor as anti-cancer treatment.

    abstract::The type 1 insulin-like growth factor receptor (IGF1R) is overexpressed by many tumors, and mediates growth, motility and protection from apoptosis. Inhibition of IGF1R expression or function has been shown to block tumor growth and metastasis, and enhance sensitivity to cytotoxic drugs and irradiation. Thus the IGF1R...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章,评审

    doi:10.1097/00001813-200310000-00001

    authors: Bohula EA,Playford MP,Macaulay VM

    更新日期:2003-10-01 00:00:00

  • Correlation of the clinical response to chemotherapy in breast cancer with ex vivo chemosensitivity.

    abstract::Chemotherapy for breast cancer is given on the basis of empirical information from clinical trials, an approach which falls to take into account the known heterogeneity of chemosensitivity between patients. Previous attempts to determine chemosensitivity ex vivo have been disappointing, but in this study results from ...

    journal_title:Anti-cancer drugs

    pub_type: 临床试验,杂志文章

    doi:10.1097/00001813-199608000-00002

    authors: Cree IA,Kurbacher CM,Untch M,Sutherland LA,Hunter EM,Subedi AM,James EA,Dewar JA,Preece PE,Andreotti PE,Bruckner HW

    更新日期:1996-08-01 00:00:00