A Licorice Roots Extract Induces Apoptosis and Cell Cycle Arrest and Improves Metabolism via Regulating MiRNAs in Liver Cancer Cells 

Abstract

Targeting altered metabolism in cancer provides a promising preventive and therapeutic approach. Natural products interplay between gene expression and metabolism either by targeting altered metabolic enzymes and/or affecting the regulating miRNAs. Licorice is a widely known product used as flavoring agent. Glycyrrhizin and other metabolites were reported to exert several metabolic benefits. Here, we investigated the effect of licorice roots extract on some metabolic pathways and their regulating miRNAs in hepatocellular carcinoma cells. Our data showed various beneficial effects of licorice roots extract including induction of apoptosis and cell cycle arrest. Second, upregulating tumor suppressor miRNAs; let7a-3p, miR-34c-5p, miR-122-5p, miR-126-3p, miR195-5p, miR-199a-5p, miR-206, and miR-326-5p. Third, inhibiting HIF1α, PI3K and C-Myc and activating AMPK and p53. Fourth, inhibiting enzymes of glycolysis; HK-2, LDH-A and PK-M2; pentose phosphate pathway; G6PD and glutaminolysis; glutaminase. However, such an extract upregulated oncogenic miRNAs; miR-21, miR-221, and miR-222. Although the present data highlights the ability of licorice roots extract to enhance apoptosis and cell cycle arrest and correct altered metabolism, it warns against its unfavorable effects, hence, its use for prevention and therapy should proceed with caution. Further experiments are required to investigate whether a specific bioactive ingredient is responsible for upregulating the oncogenic miRNAs.

Conflict of Interest

All authors declare that they have no conflict of interest.

Ethical Approval

No human or animal participation is contained in this study.

Informed Consent

No informed consent is required.

Data Availability

The authors confirm that the data supporting the findings of this study are available with the corresponding author.

Author Contribution Statement

All authors were involved in the preparation of this manuscript. Abdel-Hady A. Abdel-Wahab investigated miRNAs by RT-PCR and supervised the entire practical work and paper writing, Heba Effat performed cell cycle and apoptosis by FCM, Engy A. Mahrous provided the extract and characterized it and carried out UPLC/MS and HPLC/UV analysis, Mennatallah A. Ali performed cytotoxicity assay and statistical analyses and Tamer A. Al-Shafie performed ELISA determinations, suggested the research hypothesis and wrote the manuscript.

Additional information

Funding

This work was partially funded by a grant from Science and Technology Development Fund (STDF), Ministry of Higher Education and Scientific Research, Egypt (Grant No. 1729).