Low dose of zearalenone elevated colon cancer cell growth through G protein-coupled estrogenic receptor

Sci Rep. 2021 Apr 1;11(1):7403. doi: 10.1038/s41598-021-86788-w.


Colon cancer is one of the leading causes of cancer death worldwide. It is widely believed that environmental factors contribute to colon cancer development. Zearalenone (ZEA) is non-steroidal estrogenic mycotoxin that is widely found in the human diet and animal feeds. Most cancer studies of ZEA focused on estrogen sensitive cancers, while few focused on other types, such as colon cancer; despite the gastrointestinal tract being the first barrier exposed to food contaminants. This study investigated the stimulatory effects of ZEA on colon cancer cell lines and their underlying molecular mechanisms. ZEA promoted anchorage independent cell growth and cell cycle progression through promoting G1-to-S phase transition. Proliferative marker, cyclin D1 and Ki67 were found to be upregulated upon ZEA treatment. G protein-coupled estrogenic receptor 1 (GPER) protein expression was promoted upon ZEA treatment suggesting the involvement of GPER. The growth promoting effect mediated through GPER were suppressed by its antagonist G15. ZEA were found to promote the downstream parallel pathway, MAPK signaling pathway and Hippo pathway effector YAP1. Altogether, our observations suggest a novel mechanism by which ZEA could promote cancer growth and provide a new perspective on the carcinogenicity of ZEA.

MeSH terms

  • Active Transport, Cell Nucleus
  • Adaptor Proteins, Signal Transducing / metabolism
  • Antineoplastic Agents, Hormonal / administration & dosage*
  • Biomarkers, Tumor
  • Cell Cycle / drug effects
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism*
  • Estrogens, Non-Steroidal / administration & dosage*
  • Gene Expression
  • Humans
  • MAP Kinase Signaling System / drug effects
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism*
  • Receptors, G-Protein-Coupled / agonists
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism*
  • Transcription Factors / metabolism
  • YAP-Signaling Proteins
  • Zearalenone / administration & dosage*


  • Adaptor Proteins, Signal Transducing
  • Antineoplastic Agents, Hormonal
  • Biomarkers, Tumor
  • Estrogens, Non-Steroidal
  • GPER1 protein, human
  • Receptors, Estrogen
  • Receptors, G-Protein-Coupled
  • Transcription Factors
  • YAP-Signaling Proteins
  • YAP1 protein, human
  • Zearalenone