Enhanced anticancer effect of MAP30-S3 by cyclosproin A through endosomal escape.

Abstract:

:Cyclosporin A (CsA) is a calcium antagonist and can enhance the efficacy of some protein drugs, but its mechanism remains unknown. In this study, MAP30, a ribosome-inactivating protein reported to have apoptotic effects on cancer cells, was fused with S3, an epidermal growth factor receptor (EGFR)-targeting peptide. In addition, CsA was used to investigate whether it can further promote the apoptotic effects of S3 fused MAP30 (MAP30-S3). Our result showed that the internalization of FITC-labeled MAP30-S3 was increased significantly by S3 in HeLa cells. Unexpectedly, MAP30-S3 only showed a minor decrease in the viability of EGFR-overexpressing cancer cells, including HeLa, SMMC-7721, and MGC803 (IC50>5 μmol/l). However, 2 μmol/l CsA significantly increased the cytotoxicity of MAP30-S3, especially for HeLa cells (IC50=40.3 nmol/l). In comparison, CsA did not further decrease the cytotoxicity of MAP30-S3 on MRC-5, an EGFR low-expressing cell line from normal lung tissue, indicating that CsA did not affect the cancer-targeting specificity of MAP30-S3. Our results also showed that CsA further increased the apoptotic activity of MAP30-S3 in HeLa cells. CsA could promote the endosomal escape of FITC-MAP30-S3 with a diffused pattern in the cytoplasm. Five endocytic inhibitors were used to investigate the cellular uptake mechanism of MAP30-S3, and the results showed that the endosomal escape-enhancing effect of CsA on MAP30-S3 may be associated with the clathrin-dependent endocytic pathways. Our study suggested that CsA could be a novel endosomal escape enhancer to potentiate the intracellular release of anticancer protein drugs, resulting in their improved therapeutic efficacy.

journal_name

Anticancer Drugs

journal_title

Anti-cancer drugs

authors

Song ZT,Zhang LW,Fan LQ,Kong JW,Mao JH,Zhao J,Wang FJ

doi

10.1097/CAD.0000000000000649

subject

Has Abstract

pub_date

2018-09-01 00:00:00

pages

736-747

issue

8

eissn

0959-4973

issn

1473-5741

journal_volume

29

pub_type

杂志文章
  • Synergistic cytotoxic interaction in hormone-refractory prostate cancer with the triple combination docetaxel-erlotinib and 5-fluoro-5'-deoxyuridine.

    abstract::The current reference treatment of hormone-refractory prostate cancer consists mainly of chemotherapy with docetaxel. To improve the management of advanced prostate cancer, one should examine the benefits of adding other agents to docetaxel. We examined the growth inhibitory effects of a triple combination, including ...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/01.cad.0000224444.23953.90

    authors: Fischel JL,Ciccolini J,Formento P,Ferrero JM,Milano G

    更新日期:2006-08-01 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

  • Cyclophosphamide-induced suppressor cells in nude mice.

    abstract::Lymphocytes regenerated after treatment with a high dose of cyclophosphamide (CY) were characterized in nude mice. Ten days after a single injection of 200 mg/kg CY into nude mice, regenerated spleen cells suppressed in vitro primary and second antibody production against sheep red blood cells. The CY-treated spleen c...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/00001813-199208000-00018

    authors: Shimizu M,Sabolovic D,Ozawa H,Iwaguchi T

    更新日期:1992-08-01 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

  • Anticancer properties of thiophene derivatives in breast cancer MCF-7 cells.

    abstract::Substitutions in thiophene structure give rise to new derivatives with different biological and pharmacological activities. The present study investigated the cytotoxicity activity of some thiophene derivatives in breast cancer cells maintained in two-dimensional (2D) or in three-dimensional (3D) culture and evaluated...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0000000000000581

    authors: Dos Santos FA,Pereira MC,de Oliveira TB,Mendonça Junior FJB,de Lima MDCA,Pitta MGDR,Pitta IDR,de Melo Rêgo MJB,da Rocha Pitta MG

    更新日期:2018-02-01 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

  • 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

  • Docetaxel: an interesting new drug for the treatment of head and neck cancers and soft tissue sarcomas.

    abstract::Results are summarized for two phase II studies of docetaxel as first-line therapy for advanced squamous cell carcinoma of the head and neck (SCCHN) and one study of docetaxel as second-line therapy for advanced soft tissue sarcomas. In all three studies, docetaxel was administered at a dose of 100 mg/m2 by intravenou...

    journal_title:Anti-cancer drugs

    pub_type: 临床试验,杂志文章,多中心研究

    doi:10.1097/00001813-199507004-00004

    authors: Verweij J

    更新日期:1995-07-01 00:00:00

  • In vitro and in vivo suppression of growth of hepatocellular carcinoma cells by novel traditional Chinese medicine-platinum anti-cancer agents.

    abstract::Protein phosphatase 2A (PP2A) is a new target for platinum (Pt)-based cancer chemotherapeutic agents. A series of novel Pt complexes containing demethylcantharidin, a modified component of a traditional Chinese medicine (TCM), [Pt(C8H8O5)(NH2R)2] 1-5 have been shown to inhibit PP2A both in its purified form and in cel...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/01.cad.0000175586.31940.50

    authors: To KK,Ho YP,Au-Yeung SC

    更新日期:2005-09-01 00:00:00

  • Silibinin affects tumor cell growth because of reduction of stemness properties and induction of apoptosis in 2D and 3D models of MDA-MB-468.

    abstract::Silibinin, with a strong antioxidant activity and a weak cytotoxic property, is considered a candidate for cancer prevention. As there is no information on its effect on breast cancer tumor-initiating cells [cancer stem cells (CSCs)] in a 3D culture model, which more closely mimic natural tissues, we carried out this ...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0000000000000205

    authors: Abdollahi P,Ebrahimi M,Motamed N,Samani FS

    更新日期:2015-06-01 00:00:00

  • 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 ther...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/01.cad.0000217428.90325.35

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

    更新日期:2006-09-01 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

  • Pharmacokinetics of cabozantinib tablet and capsule formulations in healthy adults.

    abstract::Cabozantinib capsules (COMETRIQ) are approved for the treatment of patients with progressive metastatic medullary thyroid cancer. Cabozantinib tablets are investigational drug products considered to be potentially preferred pharmaceutical dosing forms. Two phase I open-label single-dose studies in healthy individuals ...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章,随机对照试验

    doi:10.1097/CAD.0000000000000366

    authors: Nguyen L,Benrimoh N,Xie Y,Offman E,Lacy S

    更新日期:2016-08-01 00:00:00

  • A phase I clinical and pharmacological study of oral 9-nitrocamptothecin, a novel water-insoluble topoisomerase I inhibitor.

    abstract::9-Nitrocamptothecin (9NC) is a water-insoluble topoisomerase I inhibitor with a broad antitumor activity in animal models. To determine the maximum tolerated oral dose (MTD), a phase I study was performed in patients with advanced cancer refractory to conventional chemotherapy. 9NC was administered orally with escalat...

    journal_title:Anti-cancer drugs

    pub_type: 临床试验,杂志文章

    doi:10.1097/00001813-199801000-00004

    authors: Verschraegen CF,Natelson EA,Giovanella BC,Kavanagh JJ,Kudelka AP,Freedman RS,Edwards CL,Ende K,Stehlin JS

    更新日期:1998-01-01 00:00:00

  • Selective distribution of aclarubicin to regional lymph nodes with a new dosage form: aclarubicin adsorbed on activated carbon particles.

    abstract::A new dosage form (ACR-CH) comprising aclarubicin adsorbed on activated carbon particles was designed to sustain release of aclarubicin. ACR-CH or aclarubicin aqueous solution (ACR-sol) was injected subcutaneously into the fore foot-pads of rats. ACR-CH distributed a statistically significantly higher level of aclarub...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/00001813-199106000-00006

    authors: Hagiwara A,Takahashi T,Iwamoto A,Yoneyama C,Matsumoto S,Muranishi S

    更新日期:1991-06-01 00:00:00

  • Baicalin induces apoptosis in SW480 cells through downregulation of the SP1 transcription factor.

    abstract::Colorectal cancer occurs throughout the world but is most common in developed countries. Cancer progression is believed to be driven by genetic mutations in this complex condition. Risk factors for developing colorectal cancer include a genetic family history, long-term ulcerative colitis, and colonic polyps. The use ...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0000000000000708

    authors: Ma W,Liu X,Du W

    更新日期:2019-02-01 00:00:00

  • Imatinib mesylate (STI571; Glivec)--a new approach in the treatment of biliary tract cancer?

    abstract::Non-resectable biliary tract cancer is associated with poor prognosis due to widespread resistance to chemotherapeutic agents and radiotherapy. It is therefore essential to explore new therapeutic approaches like the inhibition of tyrosine kinases. The aim of this study was to determine the expression of c-kit and pla...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/00001813-200310000-00011

    authors: Wiedmann M,Kreth F,Feisthammel J,Deininger M,Mössner J,Caca K

    更新日期:2003-10-01 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

  • Salvage chemotherapy with mitoxantrone and mitomycin with or without methotrexate in advanced breast cancer.

    abstract::Thirty-three patients with advanced and refractory breast cancer were treated with two mitoxantrone-containing regimens (mitoxantrone plus mitomycin and mitoxantrone plus mitomycin plus methotrexate). All patients had received previous chemotherapy with cyclophosphamide, methotrexate and fluorouracil (CMF); cyclophosp...

    journal_title:Anti-cancer drugs

    pub_type: 临床试验,杂志文章

    doi:10.1097/00001813-199210000-00004

    authors: Astone A,Cassano A,Fontana T,Noviello MR,Pozzo C,Barone C

    更新日期:1992-10-01 00:00:00

  • Intratumoral cisplatin administration in electrochemotherapy: antitumor effectiveness, sequence dependence and platinum content.

    abstract::Electrochemotherapy using intratumoral cisplatin administration was tested on EAT tumors in mice. Mice were treated with eight electric pulses (100 micros, 1 Hz, 1040 V) and/or cisplatin (1, 2, 4 and 8 mg/kg). Cisplatin treatment resulted in up to 20 days of tumor growth delay. Electrochemotherapy resulted in tumor cu...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/00001813-199807000-00002

    authors: Cemazar M,Milacic R,Miklavcic D,Dolzan V,Sersa G

    更新日期:1998-07-01 00:00:00

  • Potential antineoplastic activity of keto-C-glycosides--a new family of cytostatic agents.

    abstract::We have examined the biological activity of keto-C-glycosides (KCGs), a new family of drugs displaying antiproliferative and cytotoxic properties on tumor cells. KCG1, the most powerful drug tested on epithelial derived neoplastic cells, was 25-125 times more cytostatic on epithelial cells than on lymphoma. By contras...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/00001813-199208000-00006

    authors: Bennani-Baïti MI,Lafarge-Frayssinet C,Herscovici J,Monserret R,Antonakis K,Frayssinet C,Uriel J

    更新日期:1992-08-01 00:00:00

  • Combined treatment with pazopanib and vinflunine in patients with advanced urothelial carcinoma refractory after first-line therapy.

    abstract::The role of pazopanib in the second-line setting of refractory metastatic transitional cell carcinoma of the urothelium has not been defined clearly. The aim of this phase I/II trial was to assess the safety, tolerability, and efficacy of combining pazopanib and vinflunine in patients with metastatic transitional cell...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0b013e32835efe78

    authors: Gerullis H,Eimer C,Ecke TH,Georgas E,Arndt C,Otto T

    更新日期:2013-04-01 00:00:00

  • Exposure-response relationships in patients with metastatic renal cell carcinoma receiving sunitinib: maintaining optimum efficacy in clinical practice.

    abstract::Targeted agents such as sunitinib, an oral, multitargeted receptor tyrosine kinase inhibitor, have greatly improved the prognosis for patients with metastatic renal cell carcinoma (mRCC). In this review we analyse data from sunitinib preclinical and clinical studies in detail and consider the key implications for the ...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章,评审

    doi:10.1097/CAD.0b013e3283442039

    authors: Ravaud A,Bello CL

    更新日期:2011-06-01 00:00:00

  • Medical care consumption in a phase III trial comparing irinotecan with infusional 5-fluorouracil (5-FU) in patients with metastatic colorectal cancer after 5-FU failure.

    abstract::We evaluated economic implications of treatment with irinotecan, following a RCT which demonstrated significantly increased survival at 1 year with irinotecan (45%) compared to infusional 5-fluorouracil (5-FU) (32%) in patients with metastatic colorectal cancer. Medical care consumption data were collected prospective...

    journal_title:Anti-cancer drugs

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1097/00001813-199907000-00014

    authors: Schmitt C,Blijham G,Jolain B,Rougier P,Van Cutsem E

    更新日期:1999-07-01 00:00:00

  • Docetaxel and irinotecan (CPT-11) in the treatment of malignant pleural mesothelioma--a feasibility study.

    abstract::We chose to treat malignant pleural mesothelioma with a combination of docetaxel and irinotecan (CPT-11), because there have been preliminary reports that CPT-11 is active against mesothelioma, and docetaxel and CPT-11 were the most active agents in our in vitro experiments in human mesothelioma cell lines. Fifteen pr...

    journal_title:Anti-cancer drugs

    pub_type: 临床试验,杂志文章

    doi:10.1097/00001813-200004000-00005

    authors: Knuuttila A,Ollikainen T,Halme M,Mali P,Kivisaari L,Linnainmaa K,Jekunen A,Mattson K

    更新日期:2000-04-01 00:00:00

  • Tumour flare reaction in cancer treatments: a comprehensive literature review.

    abstract::In the past decade, tumour flare reaction (TFR) was considered as a new side effect associated with immunomodulatory agents (IMiDs) and as a condition of chronic lymphocytic leukaemia (CLL). However, this phenomenon is also observed with immune checkpoint inhibitors in solid tumours. It is still poorly understood and ...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章,评审

    doi:10.1097/CAD.0000000000000814

    authors: Taleb B A

    更新日期:2019-10-01 00:00:00

  • Norcantharidin induces anoikis through Jun-N-terminal kinase activation in CT26 colorectal cancer cells.

    abstract::Norcantharidin (NCTD), a chemically modified form of cantharidin, is a potential anticancer drug. This study investigated the effect of NCTD on anoikis in CT26 colorectal adenocarcinoma cells. NCTD treatment of CT26 cells showed a dose-dependent and time-dependent decrease in viability and cell proliferation. Growth i...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0b013e3282f18826

    authors: Chen YJ,Kuo CD,Tsai YM,Yu CC,Wang GS,Liao HF

    更新日期:2008-01-01 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

  • Radiation recall dermatitis triggered by multi-targeted tyrosine kinase inhibitors: sunitinib and sorafenib.

    abstract::Small molecule tyrosine kinase inhibitors are rapidly being integrated into the management of cancer. This is the first report of sorafenib and sunitinib, both small molecule tyrosine kinase inhibitors of vascular endothelial growth factor and platelet-derived growth factor receptors, triggering radiation recall derma...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0b013e328333d679

    authors: Chung C,Dawson LA,Joshua AM,Brade AM

    更新日期:2010-02-01 00:00:00

  • Fibroblast growth factor-inducible 14 regulates cell growth and multidrug resistance of small-cell lung cancer through the nuclear factor-κB pathway.

    abstract::Fibroblast growth factor-inducible 14 (Fn14) has been reported to play an oncogene role in many types of cancer. However, its biological functions in small-cell lung cancer (SCLC) remain unknown. The aim of this study is to investigate the roles of Fn14 in the cell growth and chemoresistance of SCLC and its possible m...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0000000000000153

    authors: Li X,Zhu W,Chen Z,Luo L,Huang J,Zhang F,Li M,Guo Y,Guo L

    更新日期:2014-11-01 00:00:00