Biology Reference
In-Depth Information
cells: downregulation of cyclins A and B1 and upregulation of cyclin E,
cell cycle arrest in S phase, induction of apoptosis
via
intrinsic pathway
(FAS-independent, caspase 8-independent) through bcl-XL
downregulation with mitochondrial release of cytochrome
c
into the
cytosol, activation of initiator caspase 9 and effector caspase 3. Neither
EA nor punicalagin induced apoptosis in normal colon CCD-112CoN
cells (no chromatin condensation and no activation of caspases 3 and 9
was detected). In the case of Caco-2 cells, no specific effect can be
attributed to punicalagin, since it was hydrolysed in the medium to yield
EA, which entered into the cells. This suggests that the anticarcinogenic
effect of punicalagin (and possibly of other ETs) could be mostly due to
their hydrolysis product EA, which induced apoptosis
via
mitochondrial
pathway in colon cancer Caco-2 cells but not in normal colon cells
(Larrosa
et al.
, 2006a). The comparison between cancer and normal cell
lines is of great interest to discard unspecific (non-desirable) cytotoxic
effects. This approach has not often been applied to this type of research
due to the difficulty in culturing normal cell lines.
There are also a number of reports regarding the
in vivo
cancer
chemopreventive activity of EA and ETs, mostly in animal models.
These studies started in the early sixties, when it was shown that EA was
able to inhibit induced lung tumours in mice upon oral administration
(Lesca, 1983). Other studies also demonstrated EA anticarcinogenic
activiy in mice (Pepin
et al.
, 1990, Castonguay
et al.
, 1997). More recent
reports have also shown that long term supplementation with dietary
doses of pomegranate fruit extracts prevented and inhibited prostate
tumours in athymic nude mice (Malik
et al.
, 2005, Malik and Mukhtar,
2006). The potential of ET-containing foodstuffs, such as blackberries,
strawberries, black raspberries, as cancer chemopreventive has been
reported. There are a number of studies that demonstrate the protection
against oral (Casto
et al.
, 2002), esophageal (Carlton
et al.
, 2001, Kresty
et al.
, 2001, Stoner
et al.
, 2006, Chen
et al.
, 2006) and colon (Harris
et
al.
, 2001) tumorigenesis in the rat. Although none of these studies clearly
identified the compound(s) responsible for these effects, the ETs seems
to be the key molecules for the cancer chemopreventive action (Ross
et
al.
, 2007). Although the majority of studies show clear effects, a recent
study reported the lack of effect of EA and ET-enriched fractions from
