6-Hydroxythiobinupharidine Inhibits Migration of LM8 Osteosarcoma Cells by Decreasing Expression of LIM Domain Kinase 1

Anticancer Res. 2019 Dec;39(12):6507-6513. doi: 10.21873/anticanres.13865.

Abstract

Background/aim: Osteosarcoma is the most malignant type of bone tumor. Patients with osteosarcoma metastases have a poorer prognosis than those without metastases. Thus, the prognosis of osteosarcoma patients with metastases must be improved.

Materials and methods: The present study investigated the inhibitory effects of 6-hydroxythiobinupharidine isolated from Nuphar pumilum on migration of LM8 murine osteosarcoma cells by a migration assay and also examined the expression of proteins related to actin dynamics by western blot. The present study also developed an automatic cell counting system using machine learning to count migrated cells by Fiji and Trainable Weka Segmentation.

Results: 6-Hydroxythiobinupharidine inhibited migration of LM8 osteosarcoma cells in a dose-dependent manner, and decreased protein expression of Lin11, Isl-1, and Mec-3 domain kinase 1 (LIMK1) and the levels of phosphorylated Cofilin.

Conclusion: 6-Hydroxythiobinupharidine suppressed migration of LM8 osteosarcoma cells by decreasing expression of LIMK1. 6-Hydroxythiobinupharidine could be potentially used as an anti-metastatic compound.

Keywords: 6-hydroxythiobinupharidine; Cofilin; LIMK; Osteosarcoma; machine learning; metastasis.

MeSH terms

  • Actin Depolymerizing Factors / metabolism
  • Animals
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Bone Neoplasms / drug therapy
  • Bone Neoplasms / metabolism*
  • Bone Neoplasms / veterinary
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic / drug effects
  • Lim Kinases / metabolism*
  • Machine Learning
  • Mice
  • Nuphar / chemistry*
  • Osteosarcoma / drug therapy
  • Osteosarcoma / metabolism*
  • Osteosarcoma / veterinary
  • Phosphorylation
  • Piperidines / chemistry
  • Piperidines / pharmacology*
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology

Substances

  • Actin Depolymerizing Factors
  • Antineoplastic Agents, Phytogenic
  • Piperidines
  • Plant Extracts
  • Lim Kinases
  • Limk1 protein, mouse