Chlorogenic acid activates ERK1/2 and inhibits proliferation of osteosarcoma cells

J Cell Physiol. 2020 Apr;235(4):3741-3752. doi: 10.1002/jcp.29269. Epub 2019 Oct 10.

Abstract

Osteosarcoma (OS) is a very aggressive metastatic pediatric and adolescent tumor. Due to its recurrent development of chemotherapy resistance, clinical outcome for OS patients remains poor. Therefore, discovering more effective anticancer agents is needed. Chlorogenic acid (CGA) is a phenolic compound contained in plant-related products that modulates many cellular functions and inhibits cell proliferation in several cancer types. However, few evidence is available in OS. Here, we investigate the effects of CGA in U2OS, Saos-2, and MG-63 OS cells. By multiple approaches, we demonstrate that CGA acts as anticancer molecule affecting the cell cycle and provoking cell growth inhibition mainly by apoptosis induction. We also provide evidence that CGA strongly activates extracellular-signal-regulated kinase1/2 (ERK1/2). Strikingly, ERK1/2 inhibitor PD98059 sensitizes the cells to CGA. Altogether, our data enforce the evidence of the anticancer activity mediated by CGA and provide the rationale for the development of innovative therapeutic strategies in OS cure.

Keywords: ERK1/2 pathway; PD98059; antitumor; apoptosis; chlorogenic acid; osteosarcoma.

MeSH terms

  • Adolescent
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • Child
  • Chlorogenic Acid / pharmacology*
  • Drug Resistance, Neoplasm / drug effects
  • Female
  • Flavonoids / pharmacology
  • Humans
  • MAP Kinase Signaling System / drug effects
  • Male
  • Mice
  • Middle Aged
  • Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 3 / genetics
  • NIH 3T3 Cells / drug effects
  • Osteosarcoma / drug therapy*
  • Osteosarcoma / genetics
  • Osteosarcoma / pathology

Substances

  • Antineoplastic Agents
  • Flavonoids
  • Chlorogenic Acid
  • MAPK3 protein, human
  • Mitogen-Activated Protein Kinase 3
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one