Curcumin Attenuates Breast Cancer Cell-induced Inflammasome Activation via the NOD-like receptor protein 3/Caspase-1/Interleukin-1β Axis.

Abstract

Breast cancer is one of the most prevalent malignancies among women worldwide; its incidence and mortality are expected to increase annually. Cancer is composed not only malignant cells but also a complex and dynamic network of interacting stromal cells, specifically immune cells, which contribute to tumor development and progression. Increasing evidence highlights the critical role of tumor-associated macrophages (TAMs) and their inflammasome-driven signaling pathways in tumor progression and therapeutic resistance. Curcumin, a natural compound with anti-carcinogenic potential, has a role in the regulation of cancer development and progression. However, its specific effects on inflammasome activation in TAMs within the tumor microenvironment (TME) remain insufficiently characterized. THP-1 monocytes differentiated into macrophages acquire the TAM-like phenotype when treated with conditioned media from breast cancer cells. Our present study aimed to investigate the effects of curcumin on inflammasome activation in macrophages induced by breast cancer-derived conditioned media. Breast cancer-derived conditioned medium stimulation induced manifestation of a pro-inflammatory TAM-like phenotype, characterized by increased interleukin (IL)-1β secretion and upregulation of NOD-like receptor protein 3 (NLRP3), caspase-1, and IL-1β. Curcumin pretreatment significantly reduced IL-1β secretion as well as NLRP3 protein levels. Moreover, it also suppressed IL1B and CASP1 mRNA expression. In conclusion, curcumin attenuates tumor-induced inflammasome activation, highlighting its potential to modulate TME-driven breast cancer progression via the NLRP3/caspase-1/IL-1β axis.