Curcumin Reprograms TAMs from a Protumor Phenotype towards an Antitumor Phenotype via Inhibiting MAO-A/STAT6 Pathway

Abstract

M1 phenotype macrophages have anticancer characteristics, whereas M2 phenotype macrophages promote tumor growth and metastasis. A higher M1/M2 ratio, therefore, has a beneficial effect on the tumor immune microenvironment, thereby inhibiting tumor growth. The natural alkaloid curcumin is found to have anticancer properties. However, the mechanism remains unclear. In this study, a cell co-culture system and M2 macrophage model were used to evaluate the effects of curcumin on tumor-associated macrophage (TAM) phenotypes. Our results demonstrate that curcumin reprogrammed the M2 macrophages by reducing the level of anti-inflammatory cytokines (TGF-β, Arg-1, and IL-10) and an M2 surface marker (CD206) induced by Cal27 cells or IL-4, as well as upregulating proinflammatory cytokines (TNF-α, iNOS, and IL-6) and an M1 surface marker (CD86). The in vitro assays suggested that curcumin treatment suppressed the migration and invasion of the Cal27 cells induced by the M2-like macrophages. Mechanistically, the repolarization of TAMs may be attributed to the inhibition of monoamine oxidase A (MAO-A)/STAT6 signaling after curcumin treatment. Collectively, our results show that the anticancer effects of curcumin could be explained by reprogramming TAMs from a protumor phenotype towards an antitumor phenotype.

Self-Augmented Reactive Oxygen Species-Responsive Nanoformulation with Efficient Curcumin Delivery for Inhibiting Triple-Negative Breast Cancer Cell Growth and Migration

“…Furthermore, this nanoformulation markedly reduced the proportion of M2 TAM (Figure D). This phenomenon can be ascribed to the curcumin-mediated disruption of the monoamine oxidase A/STAT6 signaling pathway …”

“…Recent research indicates that curcumin exerts its anticancer effects not only through modulating diverse signaling pathways but also through its immune-modulating properties. , By blocking STAT3 activity, curcumin can stimulate the production of various proinflammatory cytokines and chemokines. This mechanism allows curcumin to reverse the immunosuppressive tumor microenvironment and potentiate the antitumor effect .…”

“…This phenomenon can be ascribed to the curcumin-mediated disruption of the monoamine oxidase A/STAT6 signaling pathway. 49 3.12. Safety Evaluation.…”

The Effect of Salvianolic Acid A on Tumor-Associated Macrophage Polarization and Its Mechanisms in the Tumor Microenvironment of Triple-Negative Breast Cancer

“…Many herbal components have been shown to play a role in TAM polarization, such as andrographolide [54] and curcumin [55]; however, not much is known regarding the effects of SAA on TAMs. In our study, we hypothesized that SAA could inhibit M2-like TAM polarization from a pro-tumor phenotype to an anti-tumor phenotype after treating macrophages with a TNBC-cell-conditional medium.…”

“…TNBC cells (SUM159 or 4T1) were starved at 70% confluency for 24 h; then, the cell supernatants were collected and filtered through a 0.45 µm filter to remove cell debris and then stored at −20 • C for further use [55,57,58].…”