AI Article Synopsis
- Colorectal cancer (CRC) metastasis is influenced by M2 type tumor-associated macrophages, which play a significant role in the tumor microenvironment, and macelignan shows promise as an anticancer agent.
- Macelignan inhibits the polarization of M2 macrophages, specifically by suppressing the PI3K/AKT pathway and affecting reactive oxygen species (ROS), leading to reduced CRC metastasis in lab tests and animal studies.
- The study reveals that macelignan effectively prevents CRC metastasis through its regulation of macrophage polarization, suggesting its potential as a therapeutic option for CRC treatment.
Article Abstract
Background: 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.
Purpose: To evaluate the inhibitory potency and prospective mechanism of macelignan on M2 polarization of macrophages and CRC metastasis.
Methods: 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.
Results: 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 M2 macrophages was elevated in patients with CRC liver metastasis. Furthermore, macelignan inhibited M2 macrophage-mediated metastasis of CRC cells in vitro and in vivo. Mechanistically, macelignan reduced secretion of IL-1β from M2 macrophages, which in turn blocked NF-κB p65 nuclear translocation and inhibited metastasis.
Conclusion: 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.
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| http://dx.doi.org/10.1016/j.phymed.2023.155144 | DOI Listing |
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