TY - JOUR
T1 - Unprecedented Behavior of (9 R)-9-Hydroxystearic Acid-Loaded Keratin Nanoparticles on Cancer Cell Cycle
AU - Busi, Alberto
AU - Aluigi, Annalisa
AU - Guerrini, Andrea
AU - Boga, Carla
AU - Sartor, Giorgio
AU - Calonghi, Natalia
AU - Sotgiu, Giovanna
AU - Posati, Tamara
AU - Corticelli, Franco
AU - Fiori, Jessica
AU - Varchi, Greta
AU - Ferroni, Claudia
PY - 2019/3/4
Y1 - 2019/3/4
N2 - 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 p21 WAF1 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.
AB - 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 p21 WAF1 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.
KW - (9 R)-9-hydroxystearic acid
KW - cell cycle
KW - cell membrane
KW - drug-induced aggregation
KW - histone deacetylases
KW - keratin
KW - nanoparticles
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UR - http://www.scopus.com/inward/citedby.url?scp=85061939165&partnerID=8YFLogxK
U2 - 10.1021/acs.molpharmaceut.8b00827
DO - 10.1021/acs.molpharmaceut.8b00827
M3 - Article
C2 - 30702899
AN - SCOPUS:85061939165
VL - 16
SP - 931
EP - 942
JO - Molecular pharmaceutics
JF - Molecular pharmaceutics
SN - 1543-8384
IS - 3
ER -