3.3.2. DDA is an oxysterol with chemopreventive and
oncosuppressive properties
DDA is a mammalian metabolite present in mammalian tissue including the
breast, the levels of which decreased drastically during oncogenesis.
Tested on preclinical models of BC in immunocompetent mice, DDA was
found to inhibit the growth of aggressive syngeneic tumours at low doses
(0.035 µg/kg). This effect was observed on a chemopreventive setting and
after 10 days of post implantation of BC cells in mice. Analysis of
tumours from treated animals showed that cancer cells harboured features
of normal epithelial mammary cells, and that tumours were infiltrated
with T lymphocytes and dendritic cells (de Medina et al., 2013). This
data suggested that the immune system could contribute to the
anti-cancer action of DDA. This was further supported by the fact that
the same treatment with the same dose of DDA was inefficient to cure or
prevent BC development in immunodepressed nude mice (Sandrine
Silvente-Poirot et al, unpublished observations). It has been reported
that DDA inhibits ChEH (de Medina et al., 2013) and OCDO production in
BC cells (Voisin et al., 2017). This explains the control of OCDO
mitogenicity in vitro and in vivo in BC tumors implanted
in immunocompromised mice at DDA doses that induced ChEH inhibition
(Voisin et al., 2017). This confirmed the existence of a metabolic
balance involving on 5,6-EC and controlled by ChEH (Silvente-Poirot &
Poirot, 2014; Voisin et al., 2017). Whether the DDA/oncosterone ratio
reflects a pre-cancerous or a cancerous situation in the breast deserves
further investigations. Together these data suggest that the use of DDA
could be an interesting alternative strategy for BC treatment through a
metabolic deficiency complementation- and redifferentiation-therapy.