Stearoyl-CoA desaturase (SCD) is a central lipogenic
enzyme for the synthesis of
monounsaturated fatty acids (MUFA). SCD1 overexpression is associated with a
genetic predisposition to hepatocarcinogenesis in mice and rats. This work hypothesized possible roles of SCD1 to
genomic stability, lipogenesis, cell proliferation, and survival that contribute to the malignant transformation of non-tumorigenic liver cells. Therefore, HepG2
tumor cells were treated with the SCD1 inhibitor (
CAY10566) to ensure a decrease in proliferation/survival, as confirmed by a lipidomic analysis that detected an efficient decrease in the concentration of MUFA. According to that, we switched to a model of normal hepatocytes, the HepaRG cell line, where we: (i) overexpressed SCD1 (HepaRG-SCD1 clones), (ii) inhibited the endogenous SCD1 activity with
CAY10566, or (iii) treated with two monounsaturated (oleic OA and/or palmitoleic PA)
fatty acids. SCD1 overexpression or MUFA stimulation increased cell proliferation, survival, and the levels of AKT, phospho-AKT(Ser473), and
proliferating cell nuclear antigen (
PCNA)
proteins. By contrast, opposite molecular and cellular responses were observed in HepaRG cells treated with
CAY10566. To assess
genomic stability, HepaRG-SCD1 clones were treated with ionizing radiation (IR) and presented reduced levels of DNA damage and higher survival at doses of 5 Gy and 10 Gy compared to parental cells. In sum, this work suggests that modulation of SCD1 activity not only plays a role in cell proliferation and survival, but also in maintaining
genomic stability, and therefore, contributes to a better understanding of this
enzyme in molecular mechanisms of hepatocarcinogenesis projecting SCD1 as a potential translational target.