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Non-pungent
capsaicinoids from sweet pepper Synthesis and evaluation of the chemopreventive
and anticancer potential
Macho A, Lucena C, Sancho R, Daddario N, Minassi A,
Munoz E, Appendino G
Departamento de Biologia Celular, Fisiologia
e Inmunologia, Univ. de Cordoba, Avda de Menendez Pidal s/n, 14004, Cordoba,
Spain.
fi1muble@uco.es
Background. Capsiate, the non-pungent ester isoster of
capsaicin, and its dihydroderivative are the major capsaicinoids of sweet
peppers.
The remarkable difference between the sensory properties of capsaicin vs
capsiate is solely due to the way the vanillyl and the acyl moieties of this
basic structural motif are linked, via an amide bond in capsaicin-type compounds
and via an ester bond in capsiate-type compounds.
Ain
of the Study. Since capsaicin induces apoptosis in tumoral cells by a vanilloid
receptor type 1(VR1)-independent pathway, we examined the effects of capsiates
derived from sweet peppers in the ROS generation and induction of apoptosis in
tumoral cells and if these are mediated independently from VR1.
Methods.
We have developed an expeditious synthesis of capsiates based on the
esterification of vanillol with the Mitsunobu protocol.
Capsiate-induction of apoptosis, generation of reactive oxygen species and
disruption of the mitochondria transmembrane potential in tumoral cell lines
were measured by flow cytometry.
Chemopreventive activity was studied in a two-stage mouse skin carcinogenesis
assay.
Results.
Capsiates induce apoptosis that was preceded by an increase in the production of
reactive oxygen species and by a subsequent loss of mitochondria transmembrane
potential (DeltaPsi(m)).
These properties were retained in simplified synthetic analogues of natural
capsiates, one of which (nor-dihydrocapsiate) showed powerful chemopreventive
activity.
Conclusions.
These results suggest that capsiates and related synthetic analogues target a
variety of pathways involved in cancer development and inflammation, and have
considerable potential for dietary health benefits as well as for pharmaceutical
development.
PMID: 12594536 [PubMed - in process]
Source:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12594536&dopt=Abstract
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