7-(O)-Carboxymethyl daidzein conjugated to N-t-Boc-hexylenediamine: A novel compound capable of inducing cell death in epithelial ovarian cancer stem cells

Abstract

One of the major difficulties in the treatment of epithelial ovarian cancer (EOC) is the

high rate of recurrent disease.  This is thought to be due to the survival of a population

of chemo-resistant cells within the tumor, the ovarian cancer stem cells (OCSCs), that

are able to regenerate the tumor following chemotherapy.  Therefore, the identification

of a compund that can target the OCSCs is one of the main steps in improving overall

survival of ovarian cancer patients.   The objective of this study was to determine the

effect of N-t-boc-Daidzein, a novel daidzain derivative, on OCSCs.  The efficacy of this

compound was evaluated in OCSC and mature ovarian cancer cell (mOCC) lines

isolated from malignant ovarian cancer asicites.  Cells were treated with increasing

concentrations of N-t-boc-Daidzein (0.003-10 μM) and cell growth was monitored by

“real time in vitro micro-imaging” using the IncuCyte system.  Cell viability was

measured using the CellTiter 96 Assay.  Apoptosis was determined by Caspase-Glo

3/7, 8, and 9 assays.  The components of the apoptotic cascade were characterized by

Western blot analysis.  N-t-boc-Daidzein was able to significantly inhibit cell growth and

decrease cell viability of OCSC as well as mOCC cells in a dose and time dependent

maner.  This effect was due to the induction of apoptosis, which is characterized by

caspase activation, XIAP and AKT degradation, and mitochondrial depolarization. This

study describes a novel compound that can target the OCSCs.   These findings may

provide vital aide in improving overall survival in patients with EOC.