δ‐Tocotrienol Inhibits Migration and Reduces Chemoresistance in Ovarian Cancer Stem‐Like Cells

ABSTRACT Ovarian cancer (OC) is the most lethal form of gynecologic malignancies, due to its intrinsic chemoresistance and ability to relapse. Cancer stem cells (CSCs) are the main responsible for this fatal aggressiveness. δ‐Tocotrienol (δ‐TT) is an extensively studied anti‐tumor compound; however, its role in affecting ovarian CSC proliferation has not been elucidated yet. Herein, we demonstrated that a sphere‐forming cell population enriched in stem‐like features can be isolated from IGROV‐1 and SKOV‐3 cell lines; in particular, this subgroup was shown to possess higher migratory capacity and chemoresistance when compared to the non‐stem counterpart. Notably, δ‐TT was found to suppress OC stem‐like traits, namely clonogenic and spherogenic ability as well as embryonic marker expression and ABCG2 enrichment. In addition, it significantly disrupted the migration of OC stem‐like populations via modulation of epithelial‐to‐mesenchymal transition (EMT) and increased their sensitivity to cisplatin. At the molecular level, Akt and NF‐κB downregulation was observed in treated spheroids. Collectively, these findings highlight novel inhibitory effects of δ‐TT on OC stem‐like cells, thus offering new perspectives into its anti‐cancer potential.