Therapeutic Effects of Selenium-enriched rapeseed against Triple-Negative Breast Cancer: Involvement of Resolvin D5 Activation and IL-17 Signaling Inhibition

Abstract

Triple-negative breast cancer (TNBC) presents a major therapeutic challenge due to its aggressive behavior and a microenvironment characterized by oxidative stress and chronic inflammation. As a selenium-biofortified edible vegetable, selenium-enriched rapeseed shoots (SeRS) are a promising dietary source of methylselenocysteine (MSC), highlighting their potential in "medicine-food homology" strategies. Prior work has demonstrated that SeRS exhibits both antioxidant and anti-inflammatory properties, its precise role as a dietary intervention in modulating the redox-inflammatory axis in TNBC remains unclear. To investigate this, we evaluated the chemo-preventive efficacy of SeRS and its underlying mechanism. Our data indicate a potent inhibitory effect of the SeRS aqueous extract on both the migration and invasion of TNBC cells in a cell-based assay. In a preventive dietary regimen using a 4T1 syngeneic mouse model, SeRS potently suppressed tumor growth. Integrated metabolomic and transcriptomic analyses identified resolvin D5 (RvD5), a specialized pro-resolving mediator, as a key endogenous metabolite upregulated by SeRS, and revealed the pro-oxidant interleukin IL-17 signaling pathway as a potential target. Molecular docking confirmed high-affinity binding between RvD5 and IL-17A. Functionally, both SeRS and purified RvD5 suppressed IL-17 pathway activation, as evidenced by reduced p65 phosphorylation and downregulation of IL-17RA and ACT-1. Rescue experiments demonstrated that RvD5 could counteract IL-17A-induced tumor progression. Our findings elucidate a coordinated mechanism in which SeRS, via upregulation of RvD5, suppresses the IL-17 signaling pathway-a key driver of inflammation-associated oxidative stress-thereby exerting anti-TNBC effects. This work provides a scientific basis for developing selenium-enriched agricultural products into functional foods for cancer prevention through targeted nutritional modulation.