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Article

Transferrin-Bound Doxorubicin Enhances Apoptosis and DNA Damage through the Generation of Pro-Inflammatory Responses in Human Leukemia Cells

1
Department of Medical Biophysics, Institute of Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143 Street, 90-236 Lodz, Poland
2
Laboratory of Transcriptional Regulation, Institute for Medical Biology, PAS, Lodowa 106 Street, 93-232 Lodz, Poland
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(24), 9390; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21249390
Received: 15 November 2020 / Revised: 6 December 2020 / Accepted: 7 December 2020 / Published: 10 December 2020
Doxorubicin (DOX) is an effective antineoplastic drug against many solid tumors and hematological malignancies. However, the clinical use of DOX is limited, because of its unspecific mode of action. Since leukemia cells overexpress transferrin (Tf) receptors on their surface, we proposed doxorubicin–transferrin (DOX–Tf) conjugate as a new vehicle to increase drug concentration directly in cancer cells. The data obtained after experiments performed on K562 and CCRF-CEM human leukemia cell lines clearly indicate severe cytotoxic and genotoxic properties of the conjugate drug. On the other hand, normal peripheral blood mononuclear cells (PBMCs) were more resistant to DOX–Tf than to DOX. In comparison to free drug, we observed that Tf-bound DOX induced apoptosis in a TRAIL-dependent manner and caused DNA damage typical of programmed cell death. These fatal hallmarks of cell death were confirmed upon morphological observation of cells incubated with DOX or DOX–Tf. Studies of expression of TNF-α, IL-4, and IL-6 at the mRNA and protein levels revealed that the pro-inflammatory response plays an important role in the toxicity of the conjugate. Altogether, the results demonstrated here describe a mechanism of the antitumor activity of the DOX–Tf conjugate. View Full-Text
Keywords: leukemias; doxorubicin; inflammation leukemias; doxorubicin; inflammation
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MDPI and ACS Style

Jedrzejczyk, M.; Wisniewska, K.; Kania, K.D.; Marczak, A.; Szwed, M. Transferrin-Bound Doxorubicin Enhances Apoptosis and DNA Damage through the Generation of Pro-Inflammatory Responses in Human Leukemia Cells. Int. J. Mol. Sci. 2020, 21, 9390. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21249390

AMA Style

Jedrzejczyk M, Wisniewska K, Kania KD, Marczak A, Szwed M. Transferrin-Bound Doxorubicin Enhances Apoptosis and DNA Damage through the Generation of Pro-Inflammatory Responses in Human Leukemia Cells. International Journal of Molecular Sciences. 2020; 21(24):9390. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21249390

Chicago/Turabian Style

Jedrzejczyk, Monika, Katarzyna Wisniewska, Katarzyna D. Kania, Agnieszka Marczak, and Marzena Szwed. 2020. "Transferrin-Bound Doxorubicin Enhances Apoptosis and DNA Damage through the Generation of Pro-Inflammatory Responses in Human Leukemia Cells" International Journal of Molecular Sciences 21, no. 24: 9390. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21249390

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