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Adenosine (ADO) and its analogs have been introduced into the anticancer clinical trials, especial for the ADO derivatives with fluoride. The biosynthesis of fluorinase produces a fluorine-containing ADO analog 5 0 -fluorodeoxy adenosine (5 0 -FDA). The toxicity and application of 5 0 -FDA has not been evaluated, which limits the application of ADO analogs. In order to study its potential mechanism, we carried out the following experiments. In our research, 5 0 -FDA displayed good antitumor activity in colon cancer cells and two colon cancer models. As a result, 5 0 -FDA concentrationdependently inhibited the proliferation, migration, and invasion in colon cancer cells through its proapoptosis and cell cycle arrest pathway. Furthermore, 5 0 -FDA inhibited the growth of colon cancer and its pulmonary metastasis in CT26 inbred mice without affecting their body weight. It was found that 5 0 -FDA remarkably increased the protein levels of Caspase 3 and cleaved-Caspase 9 and decreased Cyclin A2 and CDK2 via the regulation of p53 signaling pathway, and increased the protein levels of Caspase 8 and cleaved-Caspase 8 which participated in apoptosis pathway. All in all, 5 0 -FDA displayed excellent therapeutic effects on colon cancer and its pulmonary metastasis. We believed that our study provided a theoretical basis for further preclinical research of 5 0 -FDA in the treatment of cancer.

Litchi chinensis seed, as a valuable by-product of the subtropical fruit litchi (Litchi chinensis Sonn.), has been confirmed to be rich in procyanidins (LPC). The anticarcinogenic properties of procyanidins has been primarily attributed to their antioxidant and anti-inflammatory activities. However, there is a comparative paucity of information on if and how LPC inhibits colon cancer. Here, LPC significantly inhibited CT26 colon cancer cells proliferation and metastasis in vivo and in vitro. In CT26 lung metastatic mice, the anti-metastatic effect of LPC relied on its regulation of gut microbiota such as increase of Lachnospiraceae UCG-006, Ruminococcus, and their metabolites such as acetic acid, propionic acid and butyric acid. In addition, LPC significantly inhibited CT26 colon cancer cells metastasis through increasing CD8+ cytotoxic T lymphocytes infiltration and decreasing the number of macrophages. Antibiotics treatment demonstrated that the therapeutic effect of LPC depended on the gut microbiota, which regulated T cells immune response. Taken together, LPC had strong inhibitory effects on colon cancer pulmonary metastasis by triggering gut-lung axis to influence the T cells immune response. Our research provides a novel finding for the utilization of procyanidins in the future, that is, supplementing more fruits and vegetables rich in procyanidins is beneficial to the treatment of colon cancer, or it can be used as an adjuvant drug in clinical anti-tumor immunotherapy.