In this study we focused on evaluation of the pro-oxidant properties of doxorubicin-transferrin (DOX-TRF) conjugate and its potency to damage macromolecules which are components of cellular compartments. Our experiments were performed on two human leukemia cell lines: K562 (chronic erythromyeloblastoid leukemia) and CCRF-CEM (acute lymphoblastic leukemia). We determined the reactive oxygen species (ROS) production and programmed cell death (PCD) induction by free DOX and its conjugate. Besides this, the lipid peroxidation and protein damage which can be provoked by DOX alone and DOX-TRF conjugate were assessed. ROS were produced in leukemia cells incubated with free DOX and DOX-TRF conjugate and the extent of apoptosis and necrosis was strongly dependent on the cell line, sensitivity to drug and time of incubation with the investigated compounds. The role of ROS in DOX-TRF conjugate-induced cell death was confirmed by the diminution effects of the antioxidant vitamin C.
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http://dx.doi.org/10.3109/10428194.2014.955022 | DOI Listing |
Acta Pharm Sin B
January 2018
Key Laboratory of Smart Drug Delivery, Ministry of Education, State Key Laboratory of Medical Neurobiology, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 200032, China.
Natural biomacromolecules have attracted increased attention as carriers in biomedicine in recent years because of their inherent biochemical and biophysical properties including renewability, nontoxicity, biocompatibility, biodegradability, long blood circulation time and targeting ability. Recent advances in our understanding of the biological functions of natural-origin biomacromolecules and the progress in the study of biological drug carriers indicate that such carriers may have advantages over synthetic material-based carriers in terms of half-life, stability, safety and ease of manufacture. In this review, we give a brief introduction to the biochemical properties of the widely used biomacromolecule-based carriers such as albumin, lipoproteins and polysaccharides.
View Article and Find Full Text PDFCell Oncol (Dordr)
April 2016
Department of Thermobiology, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143 Street, 90-236, Lodz, Poland.
Background: Doxorubicin (DOX) is a small molecular cytotoxic agent that can be transferred efficiently to cancer cells by nanocarriers. This anthracycline antibiotic serves as an effective anti-neoplastic drug against both hematological and solid malignancies. Here, we set out to assess the capacity of a novel doxorubicin - transferrin conjugate (DOX-TRF) to provoke apoptosis in human normal and leukemia cells through free radicals produced via a redox cycle of doxorubicin (DOX) when released from its conjugate.
View Article and Find Full Text PDFToxicol In Vitro
March 2016
Department of Thermobiology, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska St. 141/143, 90-236 Lodz, Poland. Electronic address:
The formation of reactive oxygen species (ROS) is a widely accepted mechanism of doxorubicin (DOX) toxicity toward cancer cells. However, little is known about the potential of new systems, designed for more efficient and targeted doxorubicin delivery (i.e.
View Article and Find Full Text PDFInt J Biochem Cell Biol
January 2016
Department of Thermobiology, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143 Street, 90-236 Lodz, Poland. Electronic address:
Conjugates of anthracyclines are a new possibility for anticancer agent delivery, which seems to be a very promising alternative to the currently used cancer treatment strategies. In our study, we investigated the ability of a doxorubicin-transferrin (DOX-TRF) conjugate to induce cell death in two solid tumor cell lines: non-small cell lung cancer (A549) and hepatocellular liver carcinoma (HepG2). The observed effects of the DOX-TRF conjugate on these cell cultures were compared with those of free doxorubicin (DOX), a widely used antineoplastic therapeutic agent.
View Article and Find Full Text PDFLeuk Res
October 2015
Department of Thermobiology, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143 Street, 90-236 Lodz, Poland.
Chronic myeloid leukemia (CML) is a disorder of hematopoietic stem cells caused by constitutive activation of the BCR/ABL tyrosine kinase. However, the tyrosine kinase inhibitors like imatinib mesylate are not effective in the patients with advanced-stage of CML. Hence, there is an urgent need for new approaches to overcome a cancer cell's resistance in CML long term therapy.
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