Sulforaphane inhibits thyroid cancer cell growth and invasiveness through the reactive oxygen species-dependent pathway

Oncotarget. 2015 Sep 22;6(28):25917-31. doi: 10.18632/oncotarget.4542.

Abstract

Sulforaphane (SFN), a natural compound derived from broccoli/broccoli sprouts, has been demonstrated to be used as an antitumor agent in different types of cancers. However, its antitumor effect in thyroid cancer remains largely unknown. The aim of the study was to investigate the therapeutic potential of SFN for thyroid cancer and explore the mechanisms underlying antitumor effects of SFN by in vitro and in vivo studies. Our data demonstrated that SFN significantly inhibited thyroid cancer cell proliferation in a dose- and time-dependent manner, induced G2/M phase cell cycle arrest and apoptosis, and inhibited thyroid cancer cell migration and invasion by suppressing epithelial-mesenchymal transition (EMT) process and expression of Slug, Twist, MMP-2 and -9. Mechanically, SFN inhibited thyroid cancer cell growth and invasiveness through repressing phosphorylation of Akt, enhancing p21 expression by the activation of Erk and p38 signaling cascades, and promoting mitochondrial-mediated apoptosis via reactive oxygen species (ROS)-dependent pathway. Growth of xenograft tumors derived from thyroid cancer cell line FTC133 in nude mice was also significantly inhibited by SFN. Importantly, we did not find significant effect of SFN on body weight and liver function of mice. Collectively, we for the first time demonstrate that SFN is a potentially effective antitumor agent for thyroid cancer.

Keywords: reactive oxygen species (ROS); signaling pathways; sulforaphane (SFN); thyroid cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticarcinogenic Agents / pharmacology
  • Apoptosis / drug effects
  • Apoptosis Regulatory Proteins / genetics
  • Blotting, Western
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Dose-Response Relationship, Drug
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Isothiocyanates / pharmacology*
  • Membrane Potential, Mitochondrial / drug effects
  • Mice, Nude
  • Mitogen-Activated Protein Kinases / metabolism
  • Neoplasm Invasiveness
  • Reactive Oxygen Species / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects*
  • Sulfoxides
  • Thyroid Neoplasms / drug therapy*
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / metabolism
  • Time Factors
  • Tumor Burden / drug effects
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Anticarcinogenic Agents
  • Apoptosis Regulatory Proteins
  • Isothiocyanates
  • Reactive Oxygen Species
  • Sulfoxides
  • Mitogen-Activated Protein Kinases
  • sulforaphane