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@ARTICLE{Piotto:192583,
author = {Piotto, Stefano and Concilio, Simona and Bianchino, Erminia
and Iannelli, Pio and López, David J. and Terés, Silvia
and Ibarguren, Maitane and Barceló-Coblijn, Gwendolyn and
Martin, Maria Laura and Guardiola-Serrano, Francisca and
Alonso-Sande, María and Funari, Sérgio S. and Busquets,
Xavier and Escribá, Pablo V.},
title = {{D}ifferential effect of 2-hydroxyoleic acid enantiomers on
protein (sphingomyelin synthase) and lipid (membrane)
targets},
journal = {Biochimica et biophysica acta / Biomembranes},
volume = {1838},
number = {6},
issn = {0005-2736},
address = {Amsterdam},
publisher = {Elsevier},
reportid = {PUBDB-2014-04165},
pages = {1628 - 1637},
year = {2014},
abstract = {The complex dual mechanism of action of 2-hydroxyoleic acid
(2OHOA), a potent anti-tumor compound used in membrane lipid
therapy (MLT), has yet to be fully elucidated. It has been
demonstrated that 2OHOA increases the sphingomyelin (SM)
cell content via SM synthase (SGMS) activation. Its presence
in membranes provokes changes in the membrane lipid
structure that induce the translocation of PKC to the
membrane and the subsequent overexpression of CDK inhibitor
proteins (e.g., p21(Cip1)). In addition, 2OHOA also induces
the translocation of Ras to the cytoplasm, provoking the
silencing of MAPK and its related pathways. These two
differential modes of action are triggered by the
interactions of 2OHOA with either lipids or proteins. To
investigate the molecular basis of the different
interactions of 2OHOA with membrane lipids and proteins, we
synthesized the R and S enantiomers of this compound. A
molecular dynamics study indicated that both enantiomers
interact similarly with lipid bilayers, which was further
confirmed by X-ray diffraction studies. By contrast, only
the S enantiomer was able to activate SMS in human glioma
U118 cells. Moreover, the anti-tumor efficacy of the S
enantiomer was greater than that of the R enantiomer, as the
former can act through both MLT mechanisms. The present
study provides additional information on this novel
therapeutic approach and on the magnitude of the therapeutic
effects of type-1 and type-2 MLT approaches. This article is
part of a Special Issue entitled: Membrane Structure and
Function: Relevance in the Cell's Physiology, Pathology and
Therapy.},
cin = {DOOR},
ddc = {570},
cid = {I:(DE-H253)HAS-User-20120731},
pnm = {DORIS Beamline A2 (POF2-54G13) / FS-Proposal: I-20110036 EC
(I-20110036-EC) / FS-Proposal: I-20110620 EC
(I-20110620-EC)},
pid = {G:(DE-H253)POF2-A2-20130405 / G:(DE-H253)I-20110036-EC /
G:(DE-H253)I-20110620-EC},
experiment = {EXP:(DE-H253)D-A2-20150101},
typ = {PUB:(DE-HGF)16},
UT = {WOS:000335619200017},
pubmed = {pmid:24412218},
doi = {10.1016/j.bbamem.2013.12.023},
url = {https://bib-pubdb1.desy.de/record/192583},
}