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.
Highlights
Breast cancer is an epidemic afflicting 11–12% of North American women [1]
These data clearly indicate that Gltn impairs cell cycle progression leading to S phase arrest
Our cell cycle analysis and BrdU staining revealed that Gltn reduces cell proliferation primarily via cell cyle arrest in S phase
Summary
Breast cancer is an epidemic afflicting 11–12% of North American women [1]. Breast cancer is generally stratified into four major subtypes; luminal A, luminal B, Her2+ and triple-negative. Patients with triple-negative tumors are at highest risk for recurrence and have the shortest overall survival [2]. Triple-negative patients are unresponsive to trastuzumab, or endocrine-targeting therapies due to the absence of Her and Estrogen receptor targets. Triple-negative tumors are generally targeted with surgery and traditional cytotoxic agents such as paclitaxel. Conventional chemotherapies like paclitaxel or cyclophosphamide can have severe side effects and may promote tumor progression in some cases [3,4,5]. New therapeutic strategies are needed to combat triplenegative breast cancer both at time of onset, and if necessary, at recurrence
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