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of DDA was inefficient to cure or prevent BC development in immunodepressed nude mice (Sandrine Silvente-Poirot et al, unpublished observations).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.