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

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.