Glycyrrhizic acid enhances the anticancer activity of cisplatin in the human ovarian cancer cell line

Toxicol In Vitro. 2023 Dec:93:105687. doi: 10.1016/j.tiv.2023.105687. Epub 2023 Sep 1.

Abstract

This study aimed to investigate the effects of glycyrrhizic acid (GL) on the anticancer activity of cisplatin in A2780 ovarian cancer cells. Cultured A2780 cells were treated with different concentrations of GL and cisplatin individually and in combination. The MTT assay, flow cytometry, wound-healing, and clonogenic assay, were used to determine cell viability, apoptosis, migration, and colony formation, respectively. The effects on superoxide dismutase (SOD) activity were also evaluated. QPCR was used to study the effects of individual and combined treatments with GL and cisplatin on the expression levels of migration genes (MMP2 and MMP9), and some apoptosis pathway genes (caspase-3, -8, -9, and BCL2). A synergistic effect was observed between GL and cisplatin (CI < 1). Combination therapy was significantly more effective in reducing cell viability, suppressing migration and colony formation, inducing apoptosis, and altering gene expression compared to single therapies. GL significantly increased SOD activity. The relative expression of caspase -3, -8, and - 9 increased significantly, and the expression levels of MMP2 and MMP9 decreased significantly in the treated cells. Our results indicate that GL enhances the anticancer activity of cisplatin in the A2780 cell line. Therefore, the combination of GL and cisplatin can be proposed as a promising therapeutic strategy for ovarian cancer.

Keywords: Chemotherapy; Cisplatin; Combination treatment; Glycyrrhizic acid; Ovarian cancer.

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Apoptosis
  • Cell Line, Tumor
  • Cell Proliferation
  • Cisplatin / pharmacology
  • Drug Resistance, Neoplasm
  • Female
  • Glycyrrhizic Acid / pharmacology
  • Humans
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 9 / genetics
  • Ovarian Neoplasms* / drug therapy
  • Ovarian Neoplasms* / metabolism
  • Superoxide Dismutase / genetics

Substances

  • Cisplatin
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • Glycyrrhizic Acid
  • Superoxide Dismutase
  • Antineoplastic Agents