Dark Sweet Cherry (DSC) phenolics enriched in anthocyanins suppressed the expression of genes associated with metastasis in a triple-negative breast cancer (TNBC) BALB/c mouse syngeneic model.

DSCs are a source of anthocyanins (ACNs) that have been proven to suppress tumor growth and metastasis in vitro and in vivo. TNBC metastasis is linked to genes associated with cell growth, stemness, hypoxia, and epithelial–mesenchymal transition (EMT), where epithelial cells acquire enhanced motility and invasiveness. This study assessed ACN’s role in TNBC tumors from an animal model mimicking stage-IV human BC.

4T1 TNBC cells were implanted into BALB/c mice mammary fat pads. The control group received saline solution by gavage every other day. The ACN group was fed 150mg of ACN (Cyanidin-3-O-Rutinoside) per kg body weight by gavage every other day. The DOX group received 2mg/kg body weight (I.P. injection) every 4 days, and the COMB group received both ACN and DOX at the same doses and times. Mice were euthanized when primary tumors reached 2000mm³. Tumors were analyzed for mRNA levels of genes associated with invasion and metastasis.

ACN treatment downregulated mRNA levels at 0.15-(CD44), 0.24-(HIF-1a), 0.22-(SNAI1), 0.31-(mTOR), 0.53-(RGC-32), 0.20-(SIRT1), 0.12-(STAT3), 0.14-(TGFb), and 0.18-(Tjp)-fold of control. Moreover, when compared to DOX, ACN downregulated genes linked to aberrant cell growth, EMT, and poor clinical outcomes such as CREB, HIF-1a, PIK3CA, and RGC-32 (0.04-, 0.20-, 0.05-, and 0.52-fold of DOX, respectively). Furthermore, DOX alone failed to suppress RGC-32, but COMB showed downregulation to 0.4-fold of DOX, suggesting a role of ACNs in enhancing the therapeutic efficacy of DOX.

ACNs effectively downregulated genes pivotal in TNBC metastasis, promoting angiogenesis, EMT, invasion, metabolic reprogramming, and stem cell maintenance. This suggests ACN’s potential to improve TNBC patient outcomes in chemoprevention and combination therapy. Further research is needed to investigate correlations between tumor gene expression and metastasis in harvested organs from this animal model.