Isoliquiritigenin Inhibits Ovarian Cancer Metastasis by Reversing Epithelial-to-Mesenchymal Transition

Abstract

The epithelial-to-mesenchymal transition (EMT) plays a prominent role in cancer metastasis. Isoliquiritigenin (ISL), one of the flavonoids in licorice, has been shown to exhibit anticancer activities in many cancer types through various mechanisms. However, it is unknown whether ISL impacts the EMT process. Here, we show that ISL is able to suppress mesenchymal features of ovarian cancer SKOV3 and OVCAR5 cells, evidenced by an apparent morphological change from a mesenchymal to an epithelial phenotype and reduced levels of mesenchymal markers accompanied by the gain of E-cadherin expression. The suppression of EMT is also supported by the observed decrease in cell migration and in vitro invasion upon ISL treatment. Moreover, we show that ISL effectively blocks the intraperitoneal xenograft development of the SKOV3 cell line and prolonged the survival of tumor-bearing mice. These data suggest that ISL inhibits intraperitoneal ovary tumor development through the suppression of EMT, indicating that ISL may be an effective therapeutic agent against ovarian cancer.

Isoliquiritigenin Pretreatment Induces Endoplasmic Reticulum Stress-Mediated Hormesis and Attenuates Cisplatin-Induced Oxidative Stress and Damage in LLC-PK1 Cells

“…IsoLQ is a flavonoid with anti-inflammatory, antitumoral, and antioxidant properties [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 16 , 59 ] that exerts protective effects in liver and kidney cells [ 3 , 4 , 9 , 16 , 17 , 18 ]. In addition, it has been demonstrated that IsoLQ does not interfere with CP antineoplastic activity [ 16 ].…”

“…The flavonoid 4,2′,4′-trihydroxichalcone, also known as isoliquiritigenin (IsoLQ) ( Figure 1 ), proceeds from the roots and rhizomes of licorice ( Glycyrrizha glabra ). It is used in Asia as an herbal medicine due to its anti-inflammatory, antimicrobial, antitumoral, and antioxidant properties [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 ]. Regarding its antioxidant activity, it has been reported that IsoLQ scavenges reactive oxygen species (ROS), such as the superoxide anion (O 2 ●− ), hydroxyl radical, hydrogen peroxide, and singlet oxygen [ 4 , 7 ], and induces phase II cytoprotective enzymes’ expression [ 9 , 10 ].…”

“…Regarding its antioxidant activity, it has been reported that IsoLQ scavenges reactive oxygen species (ROS), such as the superoxide anion (O 2 ●− ), hydroxyl radical, hydrogen peroxide, and singlet oxygen [ 4 , 7 ], and induces phase II cytoprotective enzymes’ expression [ 9 , 10 ]. In addition, IsoLQ has been used as an endoplasmic reticulum (ER) stress inducer in cancer cell lines to induce apoptosis [ 8 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ] and also has cytoprotective effects in non-cancer cells, such as liver and kidney cells [ 1 , 4 , 9 , 16 , 17 , 18 ].…”

Flavonoids against the Warburg phenotype—concepts of predictive, preventive and personalised medicine to cut the Gordian knot of cancer cell metabolism

“…Therapeutic strategies focused on specific cancer metabolism linked to the Warburg effect are currently under extensive consideration [174,175]. To this end, naturally occurring bioactive compounds of plants demonstrate clinically relevant beneficial effects against cancer development and progression [223][224][225][226][227][228][229][230]. The combination use of phytochemicals and chemotherapeutical drugs may represent an optimal modality for anticancer therapy [231].…”

Network Pharmacology-Based and Clinically Relevant Prediction of the Potential Targets of Chinese Herbs in Ovarian Cancer Patients

“…CHM anticancer activities are reported to be through the induction of cancer cell apoptosis, differentiation, cell cycle arrest, prevention of cancer cell growth, invasion and metastasis, and the inhibition of tumor angiogenesis [ 9 – 11 ]. Currently, CHM treats OvCa by enhancing its sensitivity to carboplain, reversing the epithelial-to-mesenchymal transition, inhibiting cancer cell proliferation, migration and invasion ability, and promoting apoptosis to control OvCa's occurrence and development [ 12 – 14 ]. Unfortunately, CHM's active ingredients and potential targets that are directly related to OvCa treatment remain unclear.…”