Isoliquiritigenin (ISL), a licorice chalconoid, is a bioactive agent with chemopreventive potential that has been
patented for tumor treatment in China. This study investigated the mechanisms of ISL-induced apoptosis in ovarian carcinoma
SKOV-3 cells. Cell viability was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide
assay. The apoptotic rate was determined via flow cytometry using an annexin V-FITC apoptosis detection kit. The intracellular
reactive oxygen species (ROS) levels were assessed using a 2,7-dichlorofluorescein probe assay. Malondialdehyde
(MDA) formation was determined via thiobarbituric acid reactive substance test. The expressions of growth arrest
and DNA damage-inducible gene (GADD153/CHOP), 78 kDa glucose-regulated protein (GRP 78), α-subunit of eukaryotic
initiation factor 2 (eIF2α) phosphorylation, activating transcription factor 6α (ATF6α), and unspliced form of X-box
binding protein1 (XBP1U) were analyzed via Western blot. Caspase-3 and caspase-12 activities were assessed using a
fluorometric kit. Findings indicate that ISL significantly inhibits SKOV-3 cell proliferation, increases intracellular ROS
levels, and causes SKOV-3 cell apoptosis. Moreover, ISL-exposed SKOV-3 cells trigger endoplasmic reticulum (ER)
stress, as indicated by the enhancement of ER stress-related molecules p-eIF2α, GADD153/CHOP, GRP78, XBP1 expression,
and cleavage of ATF6α. However, caspase-12 inhibitor (Z-ATAD) effectively and partially prevents ROS and MDA
formation and inhibits ISL-induced SKOV-3 cell apoptosis.
ISL induces apoptosis via ER stress-triggered signaling pathways in SKOV-3 cells. ER stress-induced cancer cell apoptosis
has been discussed in some patents.