Effect of Organosulfide Diallyl Trisulfide (DATS) from Garlic on Racially Different Triple Negative Breast Cancer Cells

Abstract

In triple negative breast cancer (TNBC), inflammation and immune response play a major role in the progression and metastasis of the disease. TNF‐α is a first response cytokine in the developing of the tumor and is released by macrophages to destroy the tumor due to its toxic effect on cancer cells. If TNF‐α is unable to destroy the cancer cells, macrophages begin to mimic the characteristics of cancer, eventually turning into tumor‐associated macrophages (TAM). Meanwhile, diallyl trisulfide (DATS), an organosulfide found in garlic, has previously been reported to be effective in chemoprevention, apoptosis, and cell cycle arrest in DNA damaged normal breast epithelial cells, breast cancer cells, as well as other cancers. The objective of this study is to investigate the effects of the natural compound DATS on the release of TNF‐α‐induced tumor promoting cytokines in TNBC cells, specifically MDA‐MB‐231 and MDA‐MB‐468 (representing Caucasians and African Americans, respectively), and to evaluate those specifically associated with TAM recruitment. Cell viability, cytokine arrays, and specific ELISAs were performed to investigate DATS effects on TNBC cells. In cell viability studies, DATS showed a dose‐response effect in concentrations ranging from 0–200 μM in MDA‐MB‐231 and MDA‐MB‐468 cells. Based on these results, we established a concentration of 75 μM to be used for further experimentation. The cytokine arrays showed that TNF‐α (40 ng/mL) induced the up‐regulation of monocyte chemoattractant protein‐1 (MCP‐1/CCL2) in Caucasians and African Americans cell lines; however, interleukin‐6 (IL‐6) was only up regulated in MDA‐MB‐231 cells. DATS treatment showed to be effective in inhibiting CCL2 expression in MDA‐MB‐231, but not in MDA‐MB‐468 cells. In addition, IL‐6 also showed a down regulation after DATS treatment in Caucasian cells. In order to validate the results from the arrays, ELISA quantitative assays specific for CCL2 and IL‐6 were performed. The results confirmed that TNF‐α induces expression of CCL2 expression in both breast cancer cell lines, and DATS treatment leads to the down regulation of CCL2 in MDA‐MB‐231 only, with no significant effect in MDA‐MB‐468 cells. The data from this study showed that DATS has the ability to modulate the immune response involved with TAM and cancer progression through CCL2 down regulation in MDA‐MB‐231, but not in MDA‐MB‐468 cells. These findings may also provide a better understanding of the poor therapeutic response in African American patients with TNBC.Support or Funding InformationSupported by a grant from NIMHD U54 007582