THE EFFECT OF ANNONA MURICATA LEAVES’ EXTRACT ON WNT SIGNALING PATHWAY IN INDUCED COLORECTAL CANCER IN MICE

Background: Colorectal cancer (CRC) is a significant global health issue. The Wnt signaling pathway, activated by mutations in APC and β-catenin genes, plays a crucial role in CRC development, leading to the activation of inflammatory pathways involving COX-2 and iNOS, as well as the continuous transcription of cell cycle-related genes promoting CRC pathogenesis. Annona muricata (A. muricata), a tropical tree with various biological activities, including anti-cancerous properties, was investigated for its potential effect on mice induced with colon cancer using 1,2-dimethylhydrazine (DMH, 20 mg/kg) over 12 weeks, and treated with oral A. muricata extract (100 mg/kg, 5 days/week). Methods: Histopathological analysis, qRT-PCR, ELISA and colorimetric assays were used to evaluate the effect of the extract on polyp counts, gene expression of key players of the Wnt pathway and COX-2 as well as iNOS activity, respectively. Results: Our study found that DMH-induced CRC tissues exhibited increased levels of Wnt, β-catenin, Tcf, Lef, c-Myc, Cyclin D1, COX-2, and iNOS, along with decreased APC and GSK3β expression. A. muricata extract, administered before or after treatment, significantly reversed these levels. Histopathological analysis also showed improved colonic architecture and reduced inflammatory cell infiltration with extract treatment. Conclusion: This study highlights A. muricata's potential to inhibit CRC proliferation by deactivating the Wnt signaling pathway and regulating the expression of related genes. A. muricata may serve as both a chemopreventive and therapeutic natural product for CRC.