Background/Aim: Diallyl trisulfide (DATS) has been shown to prevent and inhibit breast carcinogenesis. CCL2/MCP-1 has been shown to play a significant role in breast cancer. This study explored DATS efficacy on triple-negative breast cancer (TNBC) cells. Materials and Methods: DATS efficacy on TNFα induced TNBC cells were examined via trypan blue exclusion test, wound-healing assay, human cytokine arrays, ELISA, and RT-PCR. Results: DATS significantly induced cell death and inhibited cell migration. Expression of CCL2/MCP-1, IL-6, PDGF-BB, NT-3, and GM-CSF in TNF-α-treated cells increased. However, DATS significantly decreased the expression of CCL2/MCP-1 in TNF-α-treated MDA-MB-231 but not in MDA-MB-468 cells. DATS significantly down-regulated mRNA expression of IKBKE and MAPK8 in both cell lines, indicating a possible effect in genes involved in the NF-ĸB and MAPK signaling. Conclusion: DATS may have a role in TNBC therapy and prevention by targeting CCL2.
Garlic has long been used medicinally for many diseases, including cancer. One of the active garlic components is diallyl sulfide (DAS), which prevents carcinogenesis and reduces the incidence rate of several cancers. In this study, non-cancerous MCF-10A cells were used as a model to investigate the effect of DAS on Benzo (a)pyrene (BaP)-induced cellular carcinogenesis. The cells were evaluated based on changes in proliferation, cell cycle arrest, the formation of peroxides, 8-hydroxy-2-deoxyguanosine (8-OHdG) levels, the generation of DNA strand breaks, and DNA Polymerase β (Pol β) expression. The results obtained indicate that when co-treated with BaP, DAS inhibited BaP-induced cell proliferation (p < 0.05) to levels similar to the negative control. BaP treatment results in a two-fold increase in the accumulation of cells in the G2/M-phase of the cell cycle, which is restored to baseline levels, similar to untreated cells and vehicle-treated cells, when pretreated with 6 μM and 60 μM DAS, respectively. Co-treatment with DAS (60 μM and 600 μM) inhibited BaP-induced reactive oxygen species (ROS) formation by 132% and 133%, respectively, as determined by the accumulation of H2O2 in the extracellular medium and an increase in 8-OHdG levels of treated cells. All DAS concentrations inhibited BaP-induced DNA strand breaks through co-treatment and pre-treatment methods at all time points evaluated. Co-Treatment with 60 μM DAS increased DNA Pol β expression in response to BaP-induced lipid peroxidation and oxidative DNA damage. These results indicate that DAS effectively inhibited BaP-induced cell proliferation, cell cycle transitions, ROS, and DNA damage in an MCF-10A cell line. These results provide more experimental evidence for garlic’s antitumor abilities and corroborate many epidemiological studies regarding the association between the increased intake of garlic and the reduced risk of several types of cancer.
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.
Background/Aim: Diallyl trisulfide (DATS) has been shown to prevent and inhibit carcinogenesis in cancer cells. We have previously shown DATS's ability to decrease the percentage of viable cells, inhibit cell migration and modulate genes involved in the nuclear factor kappa-light-chainenhancer of activated B cells (NF-ĸB) and mitogen-activated protein kinase (MAPK) signaling. Materials and Methods: This study aimed to compare the efficacy of DATS in tumor necrosis factor alpha (TNF-α) induced MDA-MB-231 and MDA-MB-468 cells and investigate its role in cell-death signaling via cell cycle, flow cytometry, and caspase assay. Results: DATS exhibit a time-dependent accumulation of G 2 /M phase cells in both cell lines, with higher effects in the MDA-MB-468 for all time points. DATS's ability to decrease the percentage of viable cells in both MDA-MB-231 and MDA-MB-468 cells was shown by a significant but slight increase of early and late apoptosis in the presence of DATS comparedto control. Moreover, MDA-MB-468 cells showed more sensitivity to the DATS effect, evidenced by the higher percentage of apoptosis than MDA-MB-231 cells. The caspase studies showed a significant increase in caspase 3 and 8 activity in the presence of DATS, compared to control, in both cell lines. DATS showed no significant increase in caspase 9 activity in both cell lines compared to the control. Conclusion: DATS-induced apoptosis in human breast cancer cells is mediated, at least in part, by cell cycle arrest and caspase activity. These findings provide information for future studies into the role of DATS in TNBC therapy and prevention.
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