title: Involvement of endoplasmic reticulum stress in isoliquiritigenin-induced SKOV-3 cell apoptosis.
abstract: 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.
authors.affiliation: School of Pharmacy, Shihezi University, 832002, Shihezi, P.R. China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Yuan
authors.forename: Bacui
authors.initials: B
authors.lastname: Yu
authors.forename: Yanming
authors.initials: Y
authors.lastname: Wang
authors.forename: Jiangtao
authors.initials: J
authors.lastname: Jiang
authors.forename: Liangliang
authors.initials: L
authors.lastname: Liu
authors.forename: Hong
authors.initials: H
authors.lastname: Zhao
authors.forename: Wang
authors.initials: W
authors.lastname: Qi
authors.forename: Qiusheng
authors.initials: Q
authors.lastname: Zheng
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D047188:Chalcones / Q000494:pharmacology*; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D047188:Chalcones; D000091342:Endoplasmic Reticulum Chaperone BiP; D004791:Enzyme Inhibitors; C000717247:HSPA5 protein, human; D017382:Reactive Oxygen Species; C040920:isoliquiritigenin; D005978:Glutathione