Cytotoxic activity of G3 PAMAM-NH2 dendrimer-chlorambucil conjugate in human breast cancer cells

被引:43
作者
Bielawski, Krzysztof [1 ]
Bielawska, Anna [1 ]
Muszynska, Anna [1 ]
Poplawska, Bozena [1 ]
Czarnomysy, Robert [1 ]
机构
[1] Med Univ Bialystok, Dept Med Chem, PL-15089 Bialystok, Poland
关键词
Breast cancer; Chlorambucil; PAMAM dendrimer; Collagen biosynthesis; DRUG-DELIVERY; APOPTOSIS; ASSAY; SERA;
D O I
10.1016/j.etap.2011.08.002
中图分类号
X [环境科学、安全科学];
学科分类号
083001 [环境科学];
摘要
Evaluation of the cytotoxicity of a novel G3 PAMAM-NH2 dendrimer-chlorambucil conjugate employing a MTT assay and inhibition of [H-3]thymidine incorporation into DNA in both MDA-MB-231 and MCF-7 breast cancer cells demonstrated that the conjugate was more potent antiproliferative agent than chlorambucil. It was found that dendrimer-chlorambucil conjugate was more active inhibitor of collagen biosynthesis than chlorambucil. Our experiments carried out with flow cytometry assessment of annexin V binding and fluorescent microscopy assay revealed that PAMAM-CH conjugate inhibited the proliferation of MCF-7 and MDA-231 malignant cells by increasing the number of apoptotic and necrotic cells. The apoptotic effect of PAMAM-CH conjugate was found to be stronger than that caused by chlorambucil. (C) 2011 Elsevier B.V. All rights reserved.
引用
收藏
页码:364 / 372
页数:9
相关论文
共 32 条
[1]
Tumour and dendrimers: a review on drug delivery aspects [J].
Agarwal, Abhinav ;
Asthana, Abhay ;
Gupta, Umesh ;
Jain, Narendra K. .
JOURNAL OF PHARMACY AND PHARMACOLOGY, 2008, 60 (06) :671-688
[2]
ARMITAGE JO, 1993, CURRENT CLIN GUIDE, P37
[3]
Baker James R Jr, 2009, Hematology Am Soc Hematol Educ Program, P708, DOI 10.1182/asheducation-2009.1.708
[4]
CARMICHAEL J, 1987, CANCER RES, V47, P936
[5]
COHEN JJ, 1992, ANNU REV IMMUNOL, V10, P267, DOI 10.1146/annurev.iy.10.040192.001411
[6]
Controlling signaling with a specifically designed Gi-coupled receptor [J].
Coward, P ;
Wada, HG ;
Falk, MS ;
Chan, SDH ;
Meng, F ;
Akil, H ;
Conklin, BR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (01) :352-357
[7]
Dendrimer biocompatibility and toxicity [J].
Duncan, R ;
Izzo, L .
ADVANCED DRUG DELIVERY REVIEWS, 2005, 57 (15) :2215-2237
[8]
Polymer conjugates as anticancer nanomedicines [J].
Duncan, Ruth .
NATURE REVIEWS CANCER, 2006, 6 (09) :688-701
[9]
Farmer P.B, 1987, PHARMACOL THERAPEUT, P301
[10]
Transdominant regulation of integrin function: Mechanisms of crosstalk [J].
Gonzalez, Annette M. ;
Bhattacharya, Ramona ;
deHart, Gregory W. ;
Jones, Jonathan C. R. .
CELLULAR SIGNALLING, 2010, 22 (04) :578-583