Isoliquiritigenin Induces Autophagy and Inhibits Ovarian Cancer Cell Growth

Abstract

Ovarian cancer is one of the commonest gynecologic malignancies, which has a poor prognosis for patients at the advanced stage. Isoliquiritigenin (ISL), an active flavonoid component of the licorice plant, previously demonstrated antioxidant, anti-inflammatory, and tumor suppressive effects. In this study, we investigated the antitumor effect of ISL on human ovarian cancer in vitro using the human ovarian cancer cell lines, OVCAR5 and ES-2, as model systems. Our results show that ISL significantly inhibited the viability of cancer cells in a concentration- and time-dependent manner. Flow cytometry analysis indicated that ISL induced G2/M phase arrest. Furthermore, the expression of cleaved PARP, cleaved caspase-3, Bax/Bcl-2 ratio, LC3B-II, and Beclin-1 levels were increased in western blot analysis. To clarify the role of autophagy and apoptosis in the effect of ISL, we used the autophagy inhibitor—3-methyladenine (3-MA) to attenuate the punctate fluorescence staining pattern of the p62/sequestosome 1 (SQSTM1, red fluorescence) and LC3 (green fluorescence) proteins after ISL treatment, and 3-MA inhibited the cytotoxicity of ISL. These findings provide new information about the link between ISL-induced autophagy and apoptosis and suggest that ISL is a candidate agent for the treatment of human ovarian cancer.

Isoliquiritigenin inhibits the proliferation, migration and metastasis of Hep3B cells via suppressing cyclin D1 and PI3K/AKT pathway

“…The results of the in vivo experiment were consistent with those of the in vitro experiments, which further confirmed the effects of ISL on anti-tumor proliferation and metastasis. In conclusion, ISL may serve as a promising agent for HCC treatment, consistent with the findings from previous studies [22,23].…”

The dietary flavonoid isoliquiritigenin is a potent cytotoxin for human neuroblastoma cells

“…ISLQ is a naturally-occurring bioactive compound isolated from the roots of plants belonging to the liquorice family, with a range of biological effects that depend on the cell type and context [18]. Although the effects of ISLQ in a range of different cancers have been reported [23,26,[42][43][44][45][46][47][48], to our knowledge there has been no study that has investigated the potential of ISLQ as a cytotoxic agent for NB. This is particularly important given the poor prognosis of NB, and the fact that many NB relapses are drug resistant, while current therapies can have a range of long-term sequelae [9,10].…”

“…Flavonoids have received significant attention in this regard, not only as preventative strategies, but also as potential chemotherapeutic agents [16,17]. In particular, isoliquiritigenin (ISLQ), a chalcone-derived flavonoid naturally found in liquorice and shallots [18], has been investigated for its anticancer properties due to its potent inhibition of cell proliferation and viability in a range of cancer cell types [19][20][21][22][23][24][25][26][27][28][29]. The anticancer effects of ISLQ on NB are yet to be studied, however ISLQ has recently been found to induce cytotoxicity in the pheochromocytoma (PC-12) cell line, which, like NB, has a neural crest origin [30], suggesting that ISLQ may have anticancer effects in NB cells.…”

Dietary Compound Isoliquiritigenin, an Antioxidant from Licorice, Suppresses Triple-Negative Breast Tumor Growth via Apoptotic Death Program Activation in Cell and Xenograft Animal Models

“…MDA-MB-231 cells were maintained in Dulbecco's Modified Eagle Medium (DMEM)/F12 medium (Sigma-Aldrich, St. Louis, MO, USA) supplemented with 10% fetal bovine serum (FBS; CORNING, Manassas, VA, USA), 100 units/mL of penicillin, 100 µg/mL of streptomycin (CORNING), sodium bicarbonate (2.438 g/L; BioShop, Burlington, ON, Canada), and 4-(2-hydroxyethyl)piperazine-1-ethanesulfonic acid (HEPES; 5.986 g/L; BioShop) in a humidified incubator (37 • C, 5% CO 2 ). Dimethyl sulfoxide (DMSO) was used as a solvent of ISL, stock concentration was 100 mM, and the dosage was according to a previous study [24].…”