Lactoferrin B Combined with Antibiotics Exhibits Leukemic Selectivity and Antimicrobial Activity

Version 1 : Received: 8 December 2023 / Approved: 9 December 2023 / Online: 11 December 2023 (06:06:21 CET)
Version 2 : Received: 27 January 2024 / Approved: 29 January 2024 / Online: 29 January 2024 (08:40:14 CET)

A peer-reviewed article of this Preprint also exists.

Lica, J.J.; Gucwa, K.; Heldt, M.; Stupak, A.; Maciejewska, N.; Ptaszyńska, N.; Łęgowska, A.; Pradhan, B.; Gitlin-Domagalska, A.; Dębowski, D.; Jakóbkiewicz-Banecka, J.; Rolka, K. Lactoferricin B Combined with Antibiotics Exhibits Leukemic Selectivity and Antimicrobial Activity. Molecules 2024, 29, 678. Lica, J.J.; Gucwa, K.; Heldt, M.; Stupak, A.; Maciejewska, N.; Ptaszyńska, N.; Łęgowska, A.; Pradhan, B.; Gitlin-Domagalska, A.; Dębowski, D.; Jakóbkiewicz-Banecka, J.; Rolka, K. Lactoferricin B Combined with Antibiotics Exhibits Leukemic Selectivity and Antimicrobial Activity. Molecules 2024, 29, 678.

Abstract

The fusion of penetrating peptides (PPs) e.g., cell penetration peptides (CPP) or antimicrobial peptides (AMPs) together with aniti-micriobial agents is an expanding research field. Specific AMPs, such as Lactoferricin B (LfcinB), have demonstrated strong antibacterial, anti-fungal and antiparasitic activity, as well as valuable anticancer activity, proving beneficial in the development of anticancer conjugates. The resulting conjugates offer potential dual functionality, acting as both an anticancer and antimicrobial agent. This is particularly important in treating leukemia through hematopoietic cell transplantation (HCT), where bacterial infections are a critical risk. Crucially, leukemic cells often have altered outer lipid membranes compared to healthy cells, making them highly sensitive to compounds that interfere with their membrane. In this communication, we revisited and reanalyzed our previous work on LfcinB and its conjugates, and conducted new experiments focusing on cell proliferation, changes in membrane asymmetric phosphatidylserine location, reactive oxygen species (ROS) generation, mitochondrial functions, and in vitro bacterial topoisomerase inhibition. We found that these selected conjugates exhibit a selective cytostatic effect, against leukemia compared to healthy and tumor cell types. Importantly, these conjugates also show antimicrobial and bactericidal properties, while generating a low level of ROS and minimally affecting mitochondrial functions in human cell cultures.

Keywords

Alternative Leukemia Treatment; Antileukemic Agents; Dual-Activity Compounds; Bioconjugates; Cell Penetration Peptide; Ciprofloxacin; Hematopoietic Stem Cells Transplantation; Levofloxacin; Fluconalozle; Fluoroquinolones; LfcinB

Subject

Medicine and Pharmacology, Hematology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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