RY10-4 Inhibits the Proliferation of Human Hepatocellular Cancer HepG2 Cells by Inducing Apoptosis In Vitro and In Vivo

PLoS One. 2016 Mar 14;11(3):e0151679. doi: 10.1371/journal.pone.0151679. eCollection 2016.

Abstract

This study aimed to investigate the anti-tumor activity of RY10-4, a small molecular that was designed and synthesized based on the structure of protoapigenone. A previous screening study showed that RY10-4 possessed anti-proliferative effects against HepG2 human hepatocellular carcinoma cells. However, the full range of RY10-4 anti-cancer effects on liver tumors and the underlying mechanisms have not been identified. Herein, employing flow cytometry, and Western blot analysis, we demonstrate that RY10-4 can induce cell cycle arrest, intracellular reactive oxygen species (ROS) production and apoptosis in HepG2 cells. In HepG2 cell xenograft tumor model, RY10-4 significantly inhibited the growth of tumors and induced apoptosis in tumor cells, with little side effects. Moreover, RY10-4 caused the suppression of STAT3 activation, which may be involved the apoptosis induction. In addition, RY10-4 inhibited the proliferation of Hep3B and HuH-7 human hepatocellular carcinoma cells in a concentration-dependent manner. Taken together, our results suggest that RY10-4 has a great potential to develop as chemotherapeutic agent for liver cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects*
  • Carcinoma, Hepatocellular / pathology*
  • Cell Cycle Checkpoints / drug effects
  • Cell Proliferation / drug effects
  • Hep G2 Cells
  • Humans
  • Intracellular Space / metabolism
  • Liver Neoplasms / pathology*
  • Mice, Nude
  • Pyrones / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Xenograft Model Antitumor Assays

Substances

  • 2-(1-hydroxy-4-oxocyclohexa-2,5-dienyl)pyran-4-one
  • Antineoplastic Agents
  • Pyrones
  • Reactive Oxygen Species

Grants and funding

This work was supported by the National Natural Science Foundation of China (No. 31270390, to YYW) and the Natural Science Foundation of Hubei Province (No. 2015CFC852, to XZ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.