Laherradurin Inhibits Tumor Growth in an Azoxymethane/Dextran Sulfate Sodium Colorectal Cancer Model In Vivo

Simple Summary The complexity of the tumor cell, its ability to evade death, and its capacity to proliferate and conquer new tissues and organs make its treatment a challenge. Major challenges posed by therapeutic agents include their toxicity and consequences for patients after chemotherapy. Natural products provide a fundamental basis for the development of chemoagents. Our research aimed to test in vivo the antitumor activity of laherradurin in CRC and to measure its toxic effect. Our findings show that laherradurin inhibits growth and decreases the size of tumors in the colon compared with cisplatin. In addition, blood tests show no hepatic or renal damage or damage at the immunological level. Likewise, the disease activity index shows that those animals treated with laherradurin had diminished signs of disease. In our work, we provide new and conclusive evidence on the antitumor effect of laherradurin and measure its toxic activity under different criteria.Abstract Colorectal cancer (CRC) is the third most common neoplasia in the world. Its mortality rate is high due to the lack of specific and effective treatments, metastasis, and resistance to chemotherapy, among other factors. The natural products in cancer are a primary source of bioactive molecules. In this research, we evaluated the antitumor activity of an acetogenin (ACG), laherradurin (LH), isolated from the Mexican medicinal plant Annona macroprophyllata Donn.Sm. in a CRC murine model. The CRC was induced by azoxymethane-dextran sulfate sodium (AOM/DSS) in Balb/c mice and treated for 21 days with LH or cisplatin. This study shows for the first time the antitumor activity of LH in an AOM/DSS CRC model. The acetogenin diminished the number and size of tumors compared with cisplatin; the histologic studies revealed a recovery of the colon tissue, and the blood toxicity data pointed to less damage in animals treated with LH. The TUNEL assay indicated cell death by apoptosis, and the in vitro studies exhibited that LH inhibited cell migration in HCT116 cells. Our study provides strong evidence of a possible anticancer agent for CRC.