Gallotannin imposes S phase arrest in breast cancer cells and suppresses the growth of triple-negative tumors in vivo

PLoS One. 2014 Mar 21;9(3):e92853. doi: 10.1371/journal.pone.0092853. eCollection 2014.

Abstract

Triple-negative breast cancers are associated with poor clinical outcomes and new therapeutic strategies are clearly needed. Gallotannin (Gltn) has been previously demonstrated to have potent anti-tumor properties against cholangiocarcinoma in mice, but little is known regarding its capacity to suppress tumor outgrowth in breast cancer models. We tested Gltn for potential growth inhibitory properties against a variety of breast cancer cell lines in vitro. In particular, triple-negative breast cancer cells display higher levels of sensitivity to Gltn. The loss of proliferative capacity in Gltn exposed cells is associated with slowed cell cycle progression and S phase arrest, dependent on Chk2 phosphorylation and further characterized by changes to proliferation related genes, such as cyclin D1 (CcnD1) as determined by Nanostring technology. Importantly, Gltn administered orally or via intraperitoneal (IP) injections greatly reduced tumor outgrowth of triple-negative breast cells from mammary fat pads without signs of toxicity. In conclusion, these data strongly suggest that Gltn represents a novel approach to treat triple-negative breast carcinomas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Checkpoint Kinase 2 / metabolism
  • Cluster Analysis
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Enzyme Activation
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Hydrolyzable Tannins / administration & dosage
  • Hydrolyzable Tannins / pharmacology*
  • Mice
  • S Phase Cell Cycle Checkpoints / drug effects*
  • Triple Negative Breast Neoplasms / genetics
  • Triple Negative Breast Neoplasms / pathology*
  • Tumor Burden / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Hydrolyzable Tannins
  • Checkpoint Kinase 2