3.2.1. Oncosterone an oncometabolite and a tumour promoter in
BC
Studies on the 5,6-ECs metabolism in BC cell lines have shown that they
are metabolized into CT by ChEH and that CT was subsequently transformed
into a substance structurally characterized as the
6-oxo-cholestan-3β,5α-diol (OCDO, Oncosterone) (Fig 1C). Since ChEH is
known to be inhibited by antiproliferative substances (de Medina,
Paillasse, Segala, Poirot & Silvente-Poirot, 2010; Silvente-Poirot &
Poirot, 2012), and that CT has been reported to display certain
carcinogenic properties after oxydation (Cheng, Kang, Shih, Lo & Wang,
2005). This suggested that oncosterone could promote BC cell
proliferation. Indeed, oncosterone was shown to dose-dependently
stimulate the proliferation of human and mouse ER(+) and TNBC cell lines
suggesting a receptor-mediated effect of oncosterone. Importantly,
oncosterone was shown to stimulate the growth of BC tumours in
vivo . The inhibition of ChEH inhibited BC tumour growth, and
oncosterone addition rescued tumour growth. Together these data
establish that oncosterone is a tumour promoter. Thus blocking
oncosterone biosynthesis or neutralising oncosterone receptor(s)
provides a new rational for the pharmacological control of BC growth
which is extremely attractive especially for TNBC for which no targeted
therapy has been developed to date.
Only a few recent studies have included the dosage of oncosterone (OCDO)
in addition to other oxysterols (Dalenc et al., 2017; Iuliano et al.,
2015; Soules et al., 2017). Since 5,6-EC and CT have been linked to
several pathologies such as cancer and Niemann-Pick C1 disease, it will
be interesting to include the dosage of oncosterone in future studies to
determine its potential role in these pathologies