Stachydrine suppresses viability & migration of astrocytoma cells via CXCR4/ERK & CXCR4/Akt pathway activity

Future Oncol. 2018 Jun;14(15):1443-1459. doi: 10.2217/fon-2017-0562. Epub 2018 Jun 6.

Abstract

Aim: Pilocytic astrocytomas (PAs) are a common adolescent malignancy. We evaluated the effects of the betaine stachydrine on human PA cells as well as its associated molecular mechanism(s).

Materials & methods: Various experiments assessing stachydrine's effects on the human PA cell line Res186 were performed.

Results & conclusion: Stachydrine dose-dependently suppressed proliferation and colony formation in Res186 cells with no such effect on normal astrocytes. Stachydrine downregulated CXCR4 transcription through enhancing IκBα-based NF-κB inhibition. Stachydrine promoted apoptosis and cyclin D1/p27Kip1-associated G0/G1 phase arrest in a CXCR4/ERK- and CXCR4/Akt-dependent manner. Stachydrine suppressed MMP-associated migration and invasiveness via inhibiting CXCR4/Akt/MMP-9/2 and CXCR4/ERK/MMP-9/2 pathway activity. Stachydrine inhibits the viability, migration and invasiveness of human PA cells via inhibiting CXCR4/ERK and CXCR4/Akt signaling.

Keywords: PA; cancer; glioma; pilocytic astrocytoma; stachydrine.

MeSH terms

  • Adolescent
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects
  • Astrocytoma / drug therapy*
  • Astrocytoma / pathology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Drug Evaluation, Preclinical
  • G1 Phase Cell Cycle Checkpoints / drug effects
  • Humans
  • MAP Kinase Signaling System / drug effects*
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Neoplasm Invasiveness / prevention & control
  • Proline / analogs & derivatives*
  • Proline / pharmacology
  • Proline / therapeutic use
  • Proto-Oncogene Proteins c-akt / metabolism
  • Receptors, CXCR4 / metabolism

Substances

  • Antineoplastic Agents
  • CXCR4 protein, human
  • Receptors, CXCR4
  • Proline
  • Proto-Oncogene Proteins c-akt
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • MMP9 protein, human
  • Matrix Metalloproteinase 9
  • stachydrine