Antitumor efficacy and safety profile of gallic acid in the murine sarcoma 180 model

Abstract Gallic acid (GA) is a plant-derived polyphenol with recognized anticancer activity, but in vivo evidence, especially in mesenchymal solid tumors, remains limited. This study investigated the antitumor effects and mechanistic pathways of GA in the murine Sarcoma 180 (S-180) model. Fifty male Swiss mice bearing S-180 tumors received oral GA (10, 25, or 50 mg/kg/day), 5-fluorouracil (5-FU; 25 mg/kg, intraperitoneal), or vehicle for seven days. Tumor weight and growth inhibition were assessed, along with histopathology and immunohistochemistry for proliferation (Ki-67, a proliferation marker), apoptosis (cleaved caspase-3 and caspase-8, Bcl-2-associated X protein [Bax], and B-cell lymphoma 2 [Bcl-2]), nuclear factor kappa B (NF-κB), and systemic toxicity markers (hematological, hepatic, and renal). GA at 50 mg/kg significantly reduced tumor weight and proliferation, decreased Ki-67 and NF-κB expression, increased Bax, reduced Bcl-2, and enhanced cleaved caspase-3, indicating predominant activation of the intrinsic (mitochondrial) apoptotic pathway. Caspase-8 levels remained unchanged. Although 5-FU produced greater tumor inhibition, it induced leukopenia and splenic atrophy, whereas GA preserved hematological, hepatic, and renal parameters. These findings support GA as a promising candidate for adjuvant cancer therapy.