Histone deacetylases, HDACs, have
been demonstrated to play a critical
role in epigenetic signaling and were found to be overexpressed in
several type of cancers; therefore, they represent valuable targets
for anticancer therapy. 9-Hydroxystearic acid has been shown to bind
the catalytic site of HDAC1, inducing G0/G1 phase cell cycle arrest
and activation of the p21WAF1 gene, thus promoting cell
growth inhibition and differentiation in many cancer cells. Despite
the (R) enantiomer of 9-hydroxystearic acid (9R)
displaying a promising in vitro growth-inhibitory effect on the HT29
cell line, its scarce water solubility and micromolar activity require
novel solutions for improving its efficacy and bioavailability. In
this work, we describe the synthesis and in vitro biological profiling
of 9R keratin nanoparticles (9R@ker) obtained through an in-water
drug-induced aggregation process. The anticancer activity of 9R@ker
was investigated in the HT29 cell line; the results indicate an increased
fluidity of cell membrane and a higher intracellular ROS formation,
resulting in an unexpected S phase cell cycle arrest
(25% increase as compared to the control) induced by 9R@ker with respect
to free 9R and an induction of cell death.