Liquiritigenin Induces Tumor Cell Death through Mitogen-Activated Protein Kinase- (MPAKs-) Mediated Pathway in Hepatocellular Carcinoma Cells

Abstract

Liquiritigenin (LQ), separated from Glycyrrhiza radix, possesses anti-inflammatory, antihyperlipidemic, and antiallergic effects. Our present study aims to investigate the antihepatocellular carcinoma effects of LQ both in cell and animal models. LQ strikingly reduced cell viability, enhanced apoptotic rate, induced lactate dehydrogenase over-release, and increased intracellular reactive oxygen species (ROS) level and caspase 3 activity in both PLC/PRL/5 and HepG2 cells. The expression of cleaved PARP, the hall-marker of apoptosis, was enhanced by LQ. LQ treatment resulted in a reduction of the expressions of B-cell lymphoma 2 (Bcl-2) and B-cell lymphoma-extra large (Bcl-xL), and an increase of the phosphorylation of c-Jun N-terminal kinases (JNK) and P38. LQ-mediated cell viability reduction, mitochondrial dysfunction, apoptosis related protein abnormal expressions, and JNK and P38 activation were partially abolished by N-Acetyl-L-cysteine (a ROS inhibitor) pretreatment. Moreover, LQ suppressed the activation of extracellular signaling-regulated kinase (ERKs) and reduced the translocation of phosphor-ERKs from cytoplasm to nucleus. This antitumor activity was further confirmed in PLC/PRL/5-xenografted mice model. All these data indicate that the antihepatocellular carcinoma effects of LQ are related to its modulation of the activations of mitogen-activated protein kinase (MAPKs). The study provides experimental evidence supporting LQ as a potential therapeutic agent for hepatocellular carcinoma treatment.

Tricholoma matsutake Aqueous Extract Induces Hepatocellular Carcinoma Cell Apoptosis via Caspase-Dependent Mitochondrial Pathway

“…Bax, a proapoptotic protein, induces the threshold at which mitochondria release Cyt C to promote cell death [29]. Similarly, in another experiment, we confirmed that C. militaris induces mitochondrial apoptosis in MCF-7 and HepG2 cells related to modulation on Bcl-2 family protein expressions [30]. Oxidative stress is another factor responsible for mitochondrial function [31], during which intracellular ROS accumulation is noted.…”

Prevention of ochratoxin A‐induced oxidative stress‐mediated apoptotic processes and impairment of embryonic development in mouse blastocysts by liquiritigenin

“…In addition, ROS, especially superoxide anion (O 2 − ), the precursor of H 2 O 2 and OH − , not only activate cell death signaling processes but also induce other cytotoxic effects via protein, DNA, and lipid oxidation . Interesting, several studies have shown that LQ can either stimulate or inhibit apoptotic signaling . Importantly, our previous investigation found that preincubation of blastocysts with LQ clearly prevented citrinin‐induced apoptosis and impairments of preimplantation and postimplantation embryonic development, both in vitro and in vivo .…”

Pharmacological characterization of liquiritigenin, a chiral flavonoid in licorice

“…Anticancer activity of liquiritigenin has been observed (22). Screening for antiproliferative activity using the alamar Blue (resazurin) fluorescent cell viability measurement is relatively simple and accurate.…”

“…Previous studies have suggested some pharmacological activity for liquiritigenin including anticancer, anti-inflammatory, antidiabetic, and antioxidant activities (19202122). However, the role of each enantiomer in the pharmacological activity has not been fully evaluated.…”