Lycorine inhibits cell proliferation and migration by inhibiting ROCK1/cofilin‑induced actin dynamics in HepG2 hepatoblastoma cells

Oncol Rep. 2018 Oct;40(4):2298-2306. doi: 10.3892/or.2018.6609. Epub 2018 Jul 30.

Abstract

Lycorine, a natural alkaloid extracted from the Amaryllidaceae plant family, has been reported to exhibit anti‑cancer effects in various types of cancer cells. However, the molecular mechanisms through which lycorine exhibits anti‑hepatoblastoma activity are unclear. In the present study, the inhibitory effects of lycorine on the proliferation and migration of HepG2 hepatoblastoma cells were investigated. Lycorine inhibited the proliferation of HepG2 cells in a dose‑dependent manner by inducing cell cycle arrest at the G2/M phase, via downregulation of cyclin A, cyclin B1 and cyclin dependent kinase 1. Additionally, wound healing and Transwell assays revealed that treatment with lycorine resulted in a decrease in the migratory ability of HepG2 cells. Also, treatment with lycorine decreased the expression levels of matrix metalloproteinase (MMP)‑9 and MMP‑2. Furthermore, lycorine induced the cleavage/activation of Rho associated coiled‑coil containing protein kinase 1 (ROCK1) and the downregulation of cofilin, accompanied by an increase in polymerized filamentous actin and a loss of depolymerized globular actin. Furthermore, pre‑incubation of cells with Y‑27632, a specific ROCK1 inhibitor, markedly attenuated lycorine‑induced anti‑proliferative and anti‑migration effects. Taken together, the results demonstrated that lycorine inhibited the proliferation and migration of HepG2 cells by suppressing ROCK1/cofilin‑induced actin dynamics, which suggests that lycorine has the potential to be developed into a novel drug for hepatoblastoma treatment.

MeSH terms

  • Actins / metabolism*
  • Amaryllidaceae Alkaloids / pharmacology*
  • Apoptosis / drug effects
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Cell Cycle Checkpoints / drug effects
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects*
  • Cofilin 1 / genetics
  • Cofilin 1 / metabolism*
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Hepatoblastoma / drug therapy
  • Hepatoblastoma / metabolism
  • Hepatoblastoma / pathology*
  • Humans
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Phenanthridines / pharmacology*
  • Tumor Cells, Cultured
  • rho-Associated Kinases / genetics
  • rho-Associated Kinases / metabolism*

Substances

  • Actins
  • Amaryllidaceae Alkaloids
  • Biomarkers, Tumor
  • CFL1 protein, human
  • Cofilin 1
  • Phenanthridines
  • ROCK1 protein, human
  • rho-Associated Kinases
  • lycorine