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Authors Marcinkowska, M. ; Stanczyk, M. ; Janaszewska, A. ; Gajek, A. ; Ksiezak, M. ; Dzialak, P. ; Klajnert-Maculewicz, B.
Title Molecular mechanisms of antitumor activity of PAMAM dendrimer conjugates with anticancer drugs and a monoclonal antibody
Date 23.10.2019
Number 57252
Abstract Taxanes are considered fundamental drugs in the treatment of breast cancer, but despite the similarities, docetaxel (doc) and paclitaxel (ptx) work differently. For this reason, it is interesting to identify mechanisms of antitumor activity of PAMAM dendrimer conjugates that carry docetaxel or paclitaxel and monoclonal antibody trastuzumab, specifically targeted to cells which overexpressed HER-2. For this purpose, the impact on the level of reactive oxygen species, the mitochondrial membrane potential, cell cycle distribution and the activity of caspases-3/7, -8 and -9 of PAMAM-doc-trastuzumab and PAMAM-ptx-trastuzumab conjugates was determined and compared with free docetaxel and paclitaxel toward HER-2-positive (SKBR-3) and negative (MCF-7) human breast cancer cell lines. Moreover, apoptosis and necrosis were studied using flow cytometry and confocal microscopy, respectively. Our studies show the complexity of the potential mechanism of cytotoxic action of PAMAM-drug-trastuzumab conjugates that should be sought as a resultant of oxidative stress, mitochondrial activation of the caspase cascade and the HER-2 receptor blockade.
Publisher Polymers
Wikidata
Citation Polymers 11 (2019) 1422
DOI https://doi.org/10.3390/POLYM11091422
Tags trastuzumab taxanes tumour targeting mitochondrial membrane potential reactive oxygen species (ros) formation

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