IOSCIENCE. DO NOT DISTRIBUTE.
Background: Phytic acid is an anti-neoplastic agent. We hypothesize that during
mmary tumorigenesis, the administration of phytic acid is associated with biochemical
anges including enhancement of apoptosis and inhibition of oxidative stress.
Materials and methods: An animal model formed of 25 rats was established. The
mals were divided into three groups: (1) a control group which received the same phytic
d treatment in the right route and amount; (2) a carcinogen group which received a
cinogenic substance DMBA that can induce proliferative changes in the mammary
nd; (3) treated group which received phytic acid, 60 days after the intake of DMBA.
e animals were sacrificed, serum and tissue were evaluated for markers of tumori
nicity (serum total sialic acid, TSA); apoptotic changes (tissue caspase-3 activity and %
NA Fragmentation) and oxidative stress (tissue level of nitric oxide, NO).
Results: Following DMBA administration, benign proliferative breast changes occurred
all animals. However, these changes disappeared following phytic acid treatment. As
mpared to the control group, the development of these proliferative changes in DMBA
oup was associated with statistically significantly (p < 0.05) increased levels of TSA
d NO and decreased apoptotic activity. When compared to DMBA group, the disap
arance of the proliferative changes in phytic acid -treated group was associated with
tistically significantly (p < 0.05) decreased levels of TSA and NO and increased apop
c activity.
Conclusions: Administration of phytic acid reversed the proliferative effects of DMBA,
ggesting its protective role.
TRODUCTION
Mammary tumorigenesis is associated with alterations in both apoptotic and oxidative
ess mechanisms.1 Oxidative stress can cause DNA damage and induces mutations of
mor suppressor genes. Apoptosis is mediated by several molecules such as caspases-3 ; a
teine protease.2,3 Phytic acid (PA, Inositol hexaphosphate, IP6), a naturally occurring
osphorylated carbohydrate, is present in almost all plants (wheat germ and wheat bran)
d mammalian cells.4 Inositol can reduce cell proliferation and therefore has a antineo
stic activity. Also, it promotes differentiation of malignant cells with their reversion to
rmal phenotype.4,5 Following its administration, IP6 is taken inside the cells and
phosphorylated to lower inositol phosphate. The latter interferes with signal transduction
hways and therefore induces cell cycle arrest5. Although the antitumor effect of phytic
d was examined in breast cancer, our understanding of the biochemical and morpho
ical alterations associated with this effect is still incomplete. In this investigation, we
pothesized that during mammary tumorigenesis, the administration of phytic acid is
ociated with biochemical changes including enhancement of apoptosis and inhibition
oxidative stress. To test our hypothesis, we carried out this investigation.