A biophysical approach to daunorubicin interaction with model membranes: relevance for the drug's biological activity

• Type: Article in International Scientific Journal
• Date: 2017

Authors

Alves, AC (Author) Other; Ribeiro, D (Author) Other; Horta, M (Author) Other; Lima, JLFC (Author) FMUP; Nunes, C (Author) Other; Salette Reis (Author) FFUP

Journal

Title: Journal of the Royal Society Interface

Vol. 14

Final page: 20170408

ISSN: 1742-5689

Publisher: The Royal Society

Indexing

ISI Web of Knowledge - 2 Citations

Scopus - 12 Citations

Other information

Authenticus ID: P-00M-YY1

DOI: 10.1098/rsif.2017.0408

Abstract (EN): Daunorubicin is extensively used in chemotherapy for diverse types of cancer. Over the years, evidence has suggested that the mechanisms bywhich daunorubicin causes cytotoxic effects are also associated with interactions at the membrane level. The aim of the present work was to study the interplay between daunorubicin and mimetic membrane models composed of different ratios of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), sphingomyelin (SM) and cholesterol (Chol). Several biophysical parameters were assessed using liposomes as mimetic model membranes. Thereby, the ability of daunorubicin to partition into lipid bilayers, its apparent location within the membrane and its effect on membrane fluidity were investigated. The results showed that daunorubicin has higher affinity for lipid bilayers composed of DMPC, followed by DMPC : SM, DMPC : Chol and lastly by DMPC : SM: Chol. The addition of SM or Chol into DMPC membranes not only increases the complexity of the model membrane but also decreases its fluidity, which, in turn, reduces the amount of anticancer drug that can partition into these mimetic models. Fluorescence quenching studies suggest a broad distribution of the drug across the bilayer thickness, with a preferential location in the phospholipid tails. The gathered data support that daunorubicin permeates all types of membranes to different degrees, interacts with phospholipids through electrostatic and hydrophobic bonds and causes alterations in the biophysical properties of the bilayers, namely in membrane fluidity. In fact, a decrease in membrane fluidity can be observed in the acyl region of the phospholipids. Ultimately, such outcomes can be correlated with daunorubicin's biological action, where membrane structure and lipid composition have an important role. In fact, the results indicate that the intercalation of daunorubicin between the phospholipids can also take place in rigid domains, such as rafts that are known to be involved in different receptor processes, which are important for cellular function.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11