Annona muricata ethanolic extract protects BALB/c mice against colitis-associated colon cancer through modulation of cytokine levels and KRAS and APC expression

Annona muricata (L.) is used worldwide in folk medicine to treat numerous ailments. In vitro studies have reported that the phytocomponents of this plant have anti-inflammatory, antioxidant, and cytotoxic properties against multiple tumoral cells, including colon cancer cell lines. However, few studies have tested its antitumoral potential in vivo, especially against colitis-associated colon cancer (CAC), whose main risk factor is inflammation. This study assessed, for the first time, the protective properties of A. muricata in a murine model of CAC at the histopathological, immunological, and molecular levels. CAC was induced chemically in BALB/c mice using azoxymethane (AOM) and dextran sulfate salt (DSS). The ethanolic extract of A. muricata leaves was administered preventively or simultaneously with CAC induction. At the end of the experimental period, which lasted six months, colon and liver histopathology were assessed through hematoxylin and eosin staining. Circulating cytokines were evaluated by flow cytometry, and KRAS oncogene and APC tumor-suppressor gene expression by RT-qPCR. The ethanolic extract of A. muricata decreased circulating cytokine levels (IL-10, IL-1β, INF-γ, and IL-12) compared to the AOM-DSS group and protected colon architecture. The preventive administration of A. muricata also decreased the expression of oncogenic KRAS but increased the expression of APC tumor-suppressor mRNA in the colon of BALB/c mice. Administering A. muricata extract alone had no adverse effect on the studied parameters. Hence, our findings support the ethnobotanical use of A. muricata.