Effects of Glycyrrhizin in a Mouse Model of Lung Adenocarcinoma

Abstract

Background: Currently, there is a global attempt to identify potential anti-cancer agents with low toxicity. Previous studies have found that glycyrrhizin exerts anti-cancer action with low toxicity through suppressing thromboxane A2 (TxA2) in lung cancer cell lines. However, these effects have not yet been determined in animal models of lung cancer. Methods: Human lung adenocarcinoma xenografts were established in nude mice by the introduction of A549 cells with stable transfection of the TxA2 receptor (TPα). The animal model was confirmed by the hematoxylin and eosin (H&E) method. Tumor-bearing mice were then administered graded concentrations of glycyrrhizin, cisplatin or both. After the treatments, body weights of all animals were recorded, and immunohistochemistry staining of lung tissues and serum biochemistry detection of aspartate amino transferase (AST), alanine amino transferase (ALT), urea and creatinine were carried out. Results: Treatment with glycyrrhizin alone or the combination of cisplatin and glycyrrhizin profoundly reduced expression of thromboxane synthase (TxAS) as well as proliferating cell nuclear antigen (PCNA), recovered the body weight, and rescued damage of liver and kidney in tumor-bearing mice. Although it inhibited PCNA expression, cisplatin could not significantly suppress TxAS expression. Because of a positive feedback loop between TPα and TxAS, the effects of glycyrrhizin are possibly attributable to the suppression of the TxA2 pathway. Conclusions: This study provides in vivo evidence to support glycyrrhizin as a potential candidate for developing new regimens to overcome tumor progression and the resistance and toxicity of cisplatin.

Liquorice (Glycyrrhiza glabra): A phytochemical and pharmacological review

“…The hydromethanolic root extract of G. glabra also exhibited antimutagenic potential by suppressing micronuclei formation and chromosomal aberration in bone marrow cells of albino mice (V. Sharma, Agrawal, & Shrivastava, ). Glycyrrhizin and glycyrrhetinic acids are effective compounds in gastric cancer treatment, whereas glycyrrhizin suppresses thromboxane A2 in lung cancer cell with low toxicity (Deng, Wang, Zeng, Chen, & Huang, ). According to S. Wang et al (), 18β‐glycyrrhetinic acid has antitumour activities in breast and ovarian cancer, gastric tumours, and leukaemia.…”

Phytochemicals in Cancer Treatment: From Preclinical Studies to Clinical Practice

“…They possess complementary and overlapping mechanisms to slow down the carcinogenic process by scavenging free radicals (Lee et al, 2013), suppressing survival and proliferation of malignant cells (Yan et al, 2018), as well as diminishing invasiveness and angiogenesis of tumors (Lu et al, 2018a). They exert wide and complex range of actions on different molecular targets and signal transduction pathways including membrane receptors (Deng et al, 2017), kinases (Dou et al, 2018), downstream tumor-activator or -suppressor proteins (Adams et al, 2010), transcriptional factors (Zhang et al, 2017b), microRNAs (miRNAs) (Cojocneanu et al, 2015), cyclins, and caspases (Yan et al, 2018).…”

“…Glycyrrhizin (GA) is the major bioactive component found in licorice roots of a small leguminous shrub, Glycyrrhiza glabra L. In athymic BALB/c nude mice xenograft with human lung adenocarcinoma A549 cells stably transfected with TxA2 receptor (TPa), GA (135 mg/kg) reduced thromboxane synthase (TxAS) and proliferating cell nuclear antigen (PCNA) expression via suppressing TxA2 pathway (Deng et al, 2017). More recent findings showed that GA (100 mg/kg) inhibited the growth of non-small cell lung cancer cells (NSCLC) in patientderived xenograft (PDX) mice by suppressing the level of high mobility group box 1 (HMGB1) and inhibition of JAK/STAT signaling pathway .…”

Cytokine profile and nitric oxide levels in peritoneal macrophages of BALB/c mice exposed to Fucose-Mannose Ligand of Leishmania infantum combined with Glycyrrhizin

“…Glycyrrhizin (GL) is a natural triterpenoid saponin derived from the root of licorice (Glycyrrhiza glabra) that has been associated with numerous pharmacologic effects, including anti-bacterial, antiinflammatory, anti-oxidant, anti-viral, anti-tumor, hepatoprotective, and immunomodulatory activities (19)(20)(21)(22). Stimulation of IL-12 and NO production and suppression of IL-10 production from macrophages (23,24), augmentation of NK cell activity (23), up regulation of costimulatory molecules on dendritic cells (19), increasing of T cells proliferation, reduction of IL-4 production from T cells, direction of immune response toward Th1 (19), are the most important known immunomodulatory activities of GL.…”