Qianmei Fu

Background: Recent years have witnessed impressive growth in applying natural medicine in tumor treatment. Saffron is reported to elicit an inhibitory property against BC. Herein, we sought to explore the specific components and mechanistic basis of saffron’s anti-breast carcinoma (BC) function. Methods: Bioinformatics analysis was employed to analyze saffron components' anti-BC activity and screen the corresponding target genes involved in BC. Then, the roles of the main saffron ingredient quercetin in the activity of BC cells were examined using CCK-8, MTS, flow cytometry, colony formation, Transwell, and Gelatin zymogram assays. Additionally, the interactions among Quercetin, EET, and Stat3 were assessed by immunofluorescence and Western blot, and LC–MS/MS determined the levels of AA, EETs, and CYP3A. Finally, BC xenograft mouse models were established to verify the anti-BC function of Quercetin in vivo. Results: Quercetin, the main active component of saffron, inhibited BC progression. Quercetin suppressed BC cell growth, migration, and invasion and inhibited CYP3A4 expression and activity in BC. Mechanistically, Quercetin down-regulated CYP3A4 to block the nuclear translocation of Stat3 by decreasing the metabolization of AA to EETs, thereby alleviating BC. Moreover, exogenously added EETs counteracted the anti-tumor effect of Quercetin on BC. Quercetin also inhibited the tumor growth of tumor-bearing nude mice. Conclusion: Quercetin could inhibit the activity of CYP3A to down-regulate AA metabolites EETs, consequently hampering p-Stat3 and nuclear translocation, thus impeding BC development.

To enhance the anti-tumor immunity of macrophages by increasing iron concentration in the macrophages using nanospheres. Anti-CD206 antibody-conjugated Fe3O4-based polylactic acid glycolic acid (CD206- Fe3O4-PLGA) nanoparticles were prepared with the W/O/W method. The particle diameter was measured using Malvern particle size detector, the Zeta potential was determined using Zeta potentiometry, and the encapsulation efficiency of Fe3O4 was determined using an iron determination kit. The macrophage-binding and targeting abilities of the conjugated nanoparticles were evaluated using immunofluorescence assay, and the polarization index of macrophages was determined with Western blotting and qRT-PCR. BALB/C-57 mouse models bearing subcutaneous tumors were used to verify the efficacy of the nanoparticles to promote polarization of the tumor-associated macrophages (TAMs). The conjugated nanoparticles had a mean diameter of 260-295 nm with Zeta potential values ranging from -19 mV to -33 mV, encapsulation efficiency of Fe3O4 ranging from 65% to 75%, and anti-CD206 conjunction efficiency of 65%-70%. Immunofluorescence assay verified the targeted binding ability of the nanoparticles with M2 macrophages. Western blotting and qRT-PCR confirmed that both CD206-Fe3O4-PLGA and Fe3O4-PLGA nanoparticles promoted the expression of TNF-α, iNOS and IL-1β (P < 0.05). In the tumor-bearing mouse models, CD206-Fe3O4-PLGA nanoparticles were confirmed to promote CD86 expression in the TAMs. CD206-Fe3O4-PLGA nanoparticles are capable of targeted binding to M2 macrophages and reversing the M2 macrophages to M1 phenotype by releasing coated iron oxide particles.