Evaluating anticancer effects of geraniin supplementation in a syngeneic mouse model of breast cancer: Identification of differentially regulated plasma proteins

Abstract

Geraniin, an ellagitannin present in many seeds, nuts, fruits, and plants, has anticancer, antioxidant, antiviral, antimicrobial, antimutagenic, cardiovascular protective, and hypoglycemic properties. Geraniin was tested for its anticancer and plasma protein-modifying properties in a syngeneic mouse model of breast cancer (BC). A mouse mammary cancer cell line (4T1) was injected into the mammary pad of female BALB/c mice to produce BC. Daily oral gavage of geraniin (0.5 mg) or soy oil was given to animals having visible tumors. For 6 - 7 weeks, tumor growth was evaluated. At postmortem, cancer tissue was removed for histopathology, and the plasma was analyzed using a commercial protein array platform. Geraniin supplementation reduced tumor growth and liver metastasis (p<0.05) and altered 20 plasma proteins, including Tropomyosin 3 (TPM3), catenin beta-1 (CTNNB1), hemopoietic lineage cell-specific protein 1 (HCLS1), and Serine/threonine-protein kinase 10 (STK10). Six biomarkers (RAD23 homolog B, HCLS1, CTNNB1, A type of type ll restriction enzyme, TPM3, and STK10) were higher in geraniin-treated samples than in control samples, regardless of tumor induction. Monitoring plasma protein expression in a BC model indicated tumor progression, metastasis, and potential diagnostic or therapeutic biomarkers. The 4T1 cell line, an exceptionally invasive mammary cancer model, accurately replicates human triple-negative BC, making it valuable for investigating metastatic behavior and treatment. Plasma protein dynamics in this model may identify tumor aggressiveness regulators and therapeutic targets. Geraniin possesses antitumor and anti-metastasis characteristics and could be developed to treat BC. The autoantibody response toward these antigens and fluctuation in the response could suggest a potential marker or a predictive marker toward treatment with geraniin.

Keywords

Geraniin / Breast cancer / Mouse model / Protein array / Biomarker