TITLE:
Involvement of P Glycoprotein from Human R7 Cells Derived from Erythroleukemia in Its Attachment to the Progesterone Binding Site
AUTHORS:
S. Seddiki, H. Ould Cadi, T. Sahraoui, F. Z. El Kebir
KEYWORDS:
P Glycoprotein, Doxorubicin, Tritiated Azidopine
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.9 No.3,
March
26,
2018
ABSTRACT: Treatment of cancer with chemotherapy often faces drug resistance issues,
which can stop after a period of remission. This resistance is due to several
mechanisms; among them, the most important is the one in relation with the
overexpression of the P glycoprotein (Pgp) produced by the mdr 1 gene. This gene confers
to cells the multidrug resistance (MDR) phenotype in the setting of treatment
for many cancers (leukemia-lymphoma...). The aim of this study was to
investigate the binding site of P glycoprotein by affinity labeling in order to
synthesize effective inhibitors on chemotherapeutic drugs efflux. The first
objective was to increase P glycoprotein concentration in R7 cells by treating
them with doxorubicin to obtain human Pgp rich fractions. The second consisted
in characterizing the progesterone binding site on Pgp by affinity
photolabeling with tritiated azidopine on the one hand, and by western-blot
transfer with C219 antibody on the other hand. Our results indicate a
significant increase in the level of expression Pgp in R7 cells treated with 1
and 2.5 nM doxorubicin, and clearly show enrichment in Pgp of doxorubicin
treated R7 cells.