Salvianolic acid A, an anti-cancer agent, showed a potential effect on M2 tumor-associated macrophages in a cell culture study, which concluded that it may be useful for reprogramming these macrophages in the management of triple-negative breast cancer.
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with challenging management and a poor prognosis. The growth and metastasis of this cancer subtype are associated with the secretion of chemokines and growth factors by tumor-associated macrophages (TAMs).
Salvianolic acid A (SAA) has anti-cancer properties; however, its role in influencing TAMs in the tumor microenvironment is uncertain. This study used the human TNBC line SUM159, mouse mammary gland tumor cells, and mouse macrophage cells to investigate the role of SAA in influencing TAMs in the tumor microenvironment. The findings are published in the journal Molecules.
Tumor Microenvironment and Polarization of Macrophages
To induce the polarization of TAMs and mediate the development of the tumor microenvironment, TNBC cells were exposed to a conditioned medium (TCM-SUM159 and TCM-4T1). This medium facilitated the polarization of macrophages into M2-like TAMs.
Co-Cultured Macrophages and Expression of Growth Factors
The infiltration of M2 TAMs in cancer cells is significantly correlated with the expression of transforming growth factor beta-1 (TGF-ß1), which in turn further activates M2 TAMs. Additionally, culturing TAMs in a conditioned medium with TNBC cells also activates the extracellular signal-regulated kinase (ERK) signaling pathway.
Co-Cultured Macrophages and Expression of Cytokines
The messenger ribonucleic acid (mRNA) expression of arginase 1 (Arg-1) decreased, whereas mRNA expression of interleukin (IL)-1ß, CD86, and inducible nitric oxide synthase (iNOS) increased in the co-cultured macrophages after treatment with SAA.
Salvianolic Acid A and Inhibition of Macrophage Polarization, Migration, and Invasion
Treatment with SAA inhibited the polarization of cells into M2-like TAMs. SAA also inhibited the migration and invasion of TNBC cells by these macrophages. This was mediated by the repolarization of M2-like TAMs into M1-like TAMs.
Salvianolic Acid A and Macrophage Expression of Growth Factors
Treatment with SAA was found to be associated with a decrease in TGF-ß1 expression levels, whereas the total ERK remained unchanged. The results also indicate an increase in the expression levels of iNOS.
Source:
Tang, C., Jiang, S. Y., Li, C., Jia, X., & Yang, W. (2024). The effect of salvianolic acid A on Tumor-Associated macrophage polarization and its mechanisms in the tumor microenvironment of Triple-Negative breast Cancer. Molecules (Basel. Online), 29(7), 1469. https://doi.org/10.3390/molecules29071469
