A review on the relationship of mast cells and macrophages in breast cancer - Can herbs or natural products facilitate their anti-tumor effects?

Breast cancer is an inflammation-related cancer whose tumor microenvironment is largely infiltrated by inflammatory cells. These inflammatory cells including mast cells and macrophages have been elucidated to be vital participants in breast tumor proliferation, survival, invasion and migration. However, the functions of mast cells and macrophages in breast cancer are quite distinct based on recent data. Mast cells exhibit both anti-tumoral and pro-tumoral functions on breast cancer, while high number of tumor-associated macrophages (TAMs) are strongly correlated with poor prognosis and higher risk of distant metastasis in breast cancer patients. Besides, many natural products/extracts have been reported to regulate mast cells and macrophages. In this review, the roles of mast cells and macrophages play in breast cancer are discussed and a summary of those natural products/herbs regulating the functions of mast cells or macrophages is also presented.

Chaetolactam A, an Azaphilone Derivative from the Endophytic Fungus Chaetomium sp. g1.

Chaetolactam A (1), an unprecedented azaphilone derivative bearing a unique 9-oxa-7-azabicyclo[4.2.1]octan-8-onering system, together with two new compounds, 11-epi-chaetomugilide B (2) and chaetomugilide D (3) was isolated from an endophytic fungus, Chaetomium sp. g1. Notably, extensive NMR data analyses, NMR calculations with DP4 and DP4+ analyses, ECD calculations, and the RDC method were employed to establish the structure of 1. Furthermore, 2 exhibited potent apoptosis induction activity by mediating caspase-3 activation and PARP degradation at 3 µM in HL-60.

Natural product Eriocalyxin B suppressed triple negative breast cancer metastasis both in vitro and in vivo.

Breast cancer is the most commonly diagnosed cancer among women, and its metastasis to distant organs accounts for the majority of death. Eriocalyxin B (Eri B), an ent-kaurane diterpenoid isolating from Isodon eriocalyx var. laxiflora, has previously been reported to have anti-tumor and anti-angiogenic effects in breast cancer. Here, we investigated the effect of Eri B on cell migration and adhesion in triple negative breast cancer (TNBC) cells, as well as aldehyde dehydrogenases 1 family member A1 (ALDH1A1) expression, colony- and sphere-formation in cancer stem cell (CSC) enriched MDA-MB-231 cells. The in vivo anti-metastatic activities of Eri B were determined in 3 different breast tumor-bearing mouse models. Our results indicated that Eri B inhibited TNBC cell migration and adhesion to extracellular matrix proteins, and also reduced ALDH1A1 expression and colony formation in CSC-enriched MDA-MB-231 cells. The metastasis-related pathways, such as epidermal growth factor receptor/ mitogen-activated protein kinase kinases 1/2/ extracellular regulated protein kinase signaling altered by Eri B was firstly shown in MDA-MB-231 cells. The potent anti-metastatic efficacies of Eri B were demonstrated in breast xenograft-bearing mice and syngeneic breast tumor-bearing mice. Gut microbiome analysis results revealed the change in the diversity and composition of microbiome after Eri B treatment, and the potential pathways that are involved in the anti-cancer efficacy of Eri B. In conclusion, Eri B was shown to inhibit breast cancer metastasis in both in vitro and in vivo models. Our findings further support the development of Eri B as an anti-metastatic agent for breast cancer.