macelignan and Colorectal-Neoplasms

Colorectal cancer (CRC) metastasis is a complicated process that not only involves tumor cells but also the effects of M2 type tumor-associated macrophages, a key component of the tumor microenvironment (TME), act a crucial role in cancer metastasis. Macelignan, an orally active lignan isolated from Myristica fragrans, possesses various beneficial biological activities, including anti-cancer effects, but its effect on macrophage polarization in the TME remains unknown.. To evaluate the inhibitory potency and prospective mechanism of macelignan on M2 polarization of macrophages and CRC metastasis.. The polarization and specific mechanism of M1 and M2 macrophage regulated by macelignan were determined by western blot, flow cytometry, immunofluorescence and network pharmacology. In vitro and in vivo function assays were performed to investigate the roles of macelignan in CRC metastasis.. Macelignan efficiently inhibited IL-4/13-induced polarization of M2 macrophages by suppressing the PI3K/AKT pathway in a reactive oxygen species (ROS)-dependent manner. The proportion of CD206. Macelignan suppressed macrophage M2 polarization via ROS-mediated PI3K/AKT signaling pathway, thus preventing IL-1β/NF-κB-dependent CRC metastasis. In the present study, we reveal a previously unrecognized mechanism of macelignan in the prevention of CRC metastasis and demonstrate its effectively and safely therapeutic potential in CRC treatment.

Topics: Colorectal Neoplasms; Humans; Lignans; Macrophages; NF-kappa B; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Reactive Oxygen Species; Tumor Microenvironment