Open AccessGallotannin Imposes S Phase Arrest in Breast Cancer Cells and Suppresses the Growth of Triple-Negative Tumors In Vivo
Author(s) -
Tiejun Zhao,
Qiang Sun,
Sonia V. del Rincón,
Amanda Lovato,
Maud Marques,
Michael Witcher
Publication year - 2014
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0092853
Subject(s) - triple negative breast cancer , cancer research , breast cancer , in vivo , cyclin d1 , cell growth , cancer , cell cycle checkpoint , medicine , biology , cell cycle , genetics , microbiology and biotechnology
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.