Naturally occurring glycyrrhizin triterpene exerts anticancer effects on colorectal cancer cells via induction of apoptosis and autophagy and suppression of cell migration and invasion by targeting MMP-9 and MMP-2 expression

J BUON. 2020 Jan-Feb;25(1):188-193.

Abstract

Purpose: The main aim of the current study was to investigate the anticancer properties of naturally occurring triterpene - glycyrrhizin - against human colorectal carcinoma cells along with evaluation of its effects on cells apoptosis, autophagy and cell migration and invasion.

Methods: Cell viability was evaluated by CellTiter95® Aqueous One Solution cell viability assay, while the effects on cell apoptosis were observed by fluorescence microscopy using DAPI staining. Effects on autophagy were detected by transmission electron microscopy (TEM) along with western blot method. Transwell assay was performed to monitor the effects on cell migration and invasion.

Results: Glycyrrhizin induced selective and dose-dependent inhibition of cell growth in SW48 human colorectal carcinoma cells with lesser cytotoxicity in normal colon cells (CCD-18Co). Glycyrrhizin also led to cell apoptotic effects manifested by chromatin condensation and nuclear fragmentation as evidenced by brighter fluorescence. Apoptosis was confirmed by western blot which showed increase in Bax expression and decrease in Bcl-2 expression. TEM analysis showed that glycyrrhizin-treated cells at 12 μM showed autophagosomes indicating onset of autophagy. Western blot assay confirmed the autophagy results which showed glycyrrhizin-treated cells indicated increased expression of Beclin-1, LC3B-I and LC3B-II in a dose-dependent manner. Glycyrrhizin treatment also led to inhibition of both cell migration and invasion.

Conclusion: The results of this study reveal that glycyrrhizin can be developed as a potent anticancer agent against colorectal cancer provided further studied are performed, especially on its toxicity to humans.

MeSH terms

  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Apoptosis / drug effects*
  • Autophagy / drug effects*
  • Cell Movement / drug effects*
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / pathology
  • Glycyrrhizic Acid / pharmacology
  • Glycyrrhizic Acid / therapeutic use*
  • Humans
  • Matrix Metalloproteinase 2 / drug effects*
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / drug effects*
  • Matrix Metalloproteinase 9 / metabolism
  • Triterpenes / pharmacology
  • Triterpenes / therapeutic use*

Substances

  • Anti-Inflammatory Agents
  • Triterpenes
  • Glycyrrhizic Acid
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9