Τίτλος:
Enhancement of glioblastoma multiforme therapy through a novel Quercetin-Losartan hybrid
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Glioblastoma multiforme (GBM) is the most common and aggressive primary malignant brain tumor. Maximal
surgical resection followed by radiotherapy and concomitant chemotherapy with temozolomide remains the
first-line therapy, prolonging the survival of patients by an average of only 2.5 months. There is therefore an
urgent need for novel therapeutic strategies to improve clinical outcomes. Reactive oxygen species (ROS) are an
important contributor to GBM development. Here, we describe the rational design and synthesis of a stable
hybrid molecule tethering two ROS regulating moieties, with the aim of constructing a chemopreventive and
anticancer chemical entity that retains the properties of the parent compounds. We utilized the selective AT1R
antagonist losartan, leading to the inhibition of ROS levels, and the antioxidant flavonoid quercetin. In GBM
cells, we show that this hybrid retains the binding potential of losartan to the AT1R through competition-binding
experiments and simultaneously exhibits ROS inhibition and antioxidant capacity similar to native quercetin. In
addition, we demonstrate that the hybrid is able to alter the cell cycle distribution of GBM cells, leading to cell
cycle arrest and to the induction of cytotoxic effects. Last, the hybrid significantly and selectively reduces cancer
cell proliferation and angiogenesis in primary GBM cultures with respect to the isolated parent components or
their simple combination, further emphasizing the potential utility of the current hybridization approach in
GBM
Συγγραφείς:
A. D. Tsiailanis, A. Renziehausen, S. Kiriakidic, E. I. Vrettos,G. S. Markopoulos, N. Sayyad, B.a Hirmizf, M.I. Aguilar, M. P. Del Borgo, E. Kolettasd, R. E. Widdopg, T. Mavromoustakos, T. Crookb, N. Syedb, A. G. Tzakosa
Περιοδικό:
Free Radical Biology & Medicine
Λέξεις-κλειδιά:
Reactive oxygen species (ROS) Glioblastoma multiforme (GBM) Antioxidants AT1R AT2R Quercetin Losartan
Κύρια θεματική κατηγορία:
Θετικές Επιστήμες
DOI:
10.1016/j.freeradbiomed
Αρχείο:
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Tsiailanis_2020.pdf
6 MB
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