Influence of doxorubicin on model cell membrane properties: insights from in vitro and in silico studies

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F17%3A00478165" target="_blank" >RIV/61388963:_____/17:00478165 - isvavai.cz</a>

Result on the web

<a href="https://www.nature.com/articles/s41598-017-06445-z" target="_blank" >https://www.nature.com/articles/s41598-017-06445-z</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41598-017-06445-z" target="_blank" >10.1038/s41598-017-06445-z</a>

Result language

angličtina

Original language name

Influence of doxorubicin on model cell membrane properties: insights from in vitro and in silico studies

Original language description

Despite doxorubicin being commonly used in chemotherapy there still remain significant holes in our knowledge regarding its delivery efficacy and an observed resistance mechanism that is postulated to involve the cell membrane. One possible mechanism is the efflux by protein P-gp, which is found predominantly in cholesterol enriched domains. Thereby, a hypothesis for the vulnerability of doxorubicin to efflux through P-gp is its enhanced affinity for the ordered cholesterol rich regions of the plasma membrane. Thus, we have studied doxorubicin's interaction with model membranes in a cholesterol rich, ordered environment and in liquid-disordered cholesterol poor environment. We have combined three separate experimental protocols: UV-Vis spectrophotometry, fluorescence quenching and steady-state anisotropy and computational molecular dynamics modeling. Our results show that the presence of cholesterol induces a change in membrane structure and doesn't impair doxorubicin's membrane partitioning, but reduces drug's influence on membrane fluidity without directly interacting with it. It is thus possible that the resistance mechanism that lowers the efficacy of doxorubicin, results from an increased density in membrane regions where the efflux proteins are present. This work represents a successful approach, combining experimental and computational studies of membrane based systems to unveil the behavior of drugs and candidate drug molecules.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10403 - Physical chemistry

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2017

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Scientific Reports

ISSN

2045-2322

e-ISSN

—

Volume of the periodical

7

Issue of the periodical within the volume

Jul 24

Country of publishing house

GB - UNITED KINGDOM

Number of pages

11

Pages from-to

—

UT code for WoS article

000406260800056

EID of the result in the Scopus database

2-s2.0-85025813870