|
Antiproliferative
effect of antioxidant polyphenols from grape in murine Hepa-1c1c7
Matito C, Mastorakou F, Centelles JJ, Torres JL,
Cascante M
Department
of Peptide and Protein Chemistry, Institute for Chemical and Environmental
Research (IIQAB-CSIC), C/Jordi Girona, 18-26, 08034 Barcelona, Spain.
jltqbp@iiqab.csic.es
Background.
Grapes and wine contain high concentrations of polyphenolic compounds.
Although their cancer protective effect has been well documented, their activity
as anticarcinogens should be cautiously considered since the molecular bases of
action and their applicability to human cancer prevention are still unclear.
Aim
of the Study. We studied the antioxidant/antiradical activity and the
antiproliferative effect in vitro of different polyphenolic mixtures, extracted
from grapes and fractionated through RP-HPLC.
Methods.
The polyphenolic fractions were chemically characterized and their
antioxidant/antiradical activity was determined by the DPPH assay.
Mouse hepatoma Hepa-1c1c7 cells were used to study the cell growth inhibition
capacity of these fractions by MTT assay.
Their capacity of altering cell cycle and possible induction of apoptosis was
examined using FACS analysis.
Results.
The original polyphenolic fraction OW, which contained gallic acid (GA), (+)-catechin
(Cat), (-)-epicatechin (Ec), glycosylated flavonols (F) and procyanidin
oligomers was fractionated into fraction I, composed of monomers and small
oligomers, and fraction II that included flavonols and procyanidin oligomers of
higher molecular weight.
The three polyphenolic fractions tested showed quite similar antiradical
activity, although fraction I was the most potent antiradical agent (lowest
ED(50) value: 9 &mgr;g).
Fraction II was the least potent cell growth inhibitor (highest IC(50) value:
100 &mgr;g/ml) but showed the strongest effect on the cell cycle of
Hepa-1c1c7, inducing apoptosis in those cells.
The original fraction OW was demonstrated to have the most potent cell growth
inhibition effect (lowest IC(50) value: 43 &mgr;g/ml).
However, it only appeared to alter cell cycle of Hepa-1c1c7 at concentrations
higher than its IC(50) and did not induce apoptosis in those cells.
A similar effect on cell cycle and apoptosis was encountered for fraction I.
Conclusions.
The polyphenolic fractions tested in this study were potent antiradical agents
and exerted an antiproliferative effect in mouse hepatoma Hepa-1c1c7 cells; the
fraction with the highest degree of polimerization and galloylation (fraction
II) had the most influence on the cell cycle and induction of apoptosis on
Hepa-1c1c7.
PMID: 12594540 [PubMed - as supplied by publisher]
Source:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12594540&dopt=Abstract
|
