Effects of Diallyl Trisulfide on TNF-alpha-stimulated Genetically different Triple-Negative Breast Cancer Cells

Many studies have demonstrated the potential anticancer properties of garlic and their respective constituents through in vitro and in vivo studies. Diallyl trisulfide (DATS), an organosulfur compound of garlic, has been shown to prevent and inhibit breast carcinogenesis through various signaling pathways. The triple-negative breast cancer (TNBC) subtype, which accounts for approximately 15% of all breast cancers, usually behaves more aggressively than other types of breast cancer and is more challenging to treat. Cancer progression is associated with the overexpression of the monocyte chemotactic protein-1 (MCP-1. MCP-1, also known as C-C motif chemokine ligand-2 (CCL2), plays a significant role in breast cancer cell signaling, leading to increased cell proliferation, immune suppression, epithelial-to-mesenchymal transition (EMT), and angiogenesis. This study explored DATS effects on the genetically different triple-negative breast cancer cells, MDA-MB-231 and MDA-MB-468. DATS effects on TNF-α induced TNBC cells were examined via trypan blue exclusion test, wound-healing assay, human cytokine arrays, ELISA, and RT-PCR. The results showed that DATS induced cytotoxicity in a dose and time-response way in MDA-MB-231 and MDA-MB-468 cell lines. Wound healing assays demonstrated that DATS significantly inhibited cell migration after a 12 h exposure in both cell lines. Protein expression of CCL2/MCP-1, IL-6, PDGF-BB, NT-3, and GM-CSF was increased in the TNF-α-treated cells. However, the cotreatment with DATS and TNF-α showed that the compound significantly decreased the expression of CCL2/MCP-1 in MDA-MB-231 but not in MDA-MB-468 cells; data confirmed with ELISA. Moreover, DATS significantly down-regulated mRNA expression of IKBKE and MAPK8 in both cell lines, indicating a possible effect in genes involved in the NF-κB and MAPK signaling. The data show that genetically different cells may respond in a different way to DATS treatment. In conclusion, DATS may be a potential candidate for breast cancer therapy to slow TNBC progression.