Cellular effects of Ferula Assafoetida on breast cancer cells and inflammatory responses in cultured monocytes

Abstract

In traditional medicine, Ferula assafoetida (F. assafoetida), has been used as an antiseptic, anti-diabetic, anti-inflammatory, and anti-cancer agent. In recent years its anti-cancer and antiinflammatory activities have become a focus in drug research. We investigated the in vitro cytotoxicity and anti-inflammatory effects of ethanolic extracts of F. assafoetida and five known components (ferulic acid, vanillic acid, quercetin, ellagic acid, and p-coumaric acid) on a group of malignant and non-malignant breast cell lines and the THP-1 monocyte-like cell line. Our results showed that treatment with the ethanolic extract of F. assafoetida, and the components, had a significant effect on cell viability and apoptosis induction for the human MCF-7, MDA-MB-231, and murine 4T1 breast cancer cell lines compared to the non-malignant human HBL-100 breast cells. This research also showed that THP-1 peripheral blood monocytic leukemia cells, differentiated into macrophages, could be further polarized into the M1 inflammatory phenotype by treatment with extracts of F. assafoetida and the components. There was a significant increase in the expression of CD80, a marker associated with the M1 macrophage subtype, but no increase in expression of the M2 subtype marker, CD163, in treated cells. Further, this polarization of the THP-1-dependent macrophages showed an increased ability to damage MCF-7 or MDA-MB-231 cell monolayers in co-culture experiments. Therefore, treatment with F. assafoetida extracts can also indirectly cause the death of cancer cells via activation of immune cells. These results confirm that F. assafoetida is a potential source of anti-cancer and immune modulatory compounds and that further investigation is needed to reveal the mechanisms of F. assafoetida’s effects on apoptosis and immunomodulation. Keywords: Ferula assafoetida, anti-cancer, pro-inflammation, cytotoxicity, apoptosis immunomodulation, macrophage polarization