Antimetastatic Therapies of the Polysulfide Diallyl Trisulfide against Triple-Negative Breast Cancer (TNBC) via Suppressing MMP2/9 by Blocking NF-κB and ERK/MAPK Signaling Pathways

Abstract

BackgroundMigration and invasion are two crucial steps of tumor metastasis. Blockage of these steps may be an effective strategy to reduce the risk. The objective of the present study was to investigate the effects of diallyl trisulfide (DATS), a natural organosulfuric compound with most sulfur atoms found in garlic, on migration and invasion in triple negative breast cancer (TNBC) cells. Molecular mechanisms underlying the anticancer effects of DATS were further investigated.Methods and ResultsMDA-MB-231 cells and HS 578t breast cancer cells were treated with different concentrations of DATS. DATS obviously suppressed the migration and invasion of two cell lines and changed the morphological. Moreover, DATS inhibited the mRNA/protein/ enzymes activities of MMP2/9 via attenuating the NF-κB pathway. DATS also inhibited ERK/MAPK rather than p38 and JNK.ConclusionDATS inhibits MMP2/9 activity and the metastasis of TNBC cells, and emerges as a potential anti-cancer agent. The inhibitory effects are associated with down-regulation of the transcriptional activities of NF-κB and ERK/MAPK signaling pathways.

Effect of miR-146a-5p on proliferation and metastasis of triple-negative breast cancer via regulation of SOX5

“…Previously, great improvements have been made in the early detection and treatment of breast cancer. However, due to sub-optimal hormonal therapy and a lack of more specific and effective therapeutic targets, TNBC treatment remains a challenge (5,6). Thus, identifying biological markers of TNBC progress is necessary and could provide novel therapeutic strategies for TNBC treatment.…”

Associations of Promoter Methylations and mRNA Expressions of <b><i>MMP-2</i></b>, <b><i>MMP-7</i></b> and <b><i>MMP-9</i></b> with Primary Fallopian Tube Carcinoma

“…By blocking NF-κB and ERK/MAPK signaling pathways, both MMP-2 and MMP-9 weaken the migration and invasion abilities of carcinoma cells. This can further prove that MMP-2 and MMP-9 methylations can serve as independent risk factors for PFTC prognoses [27,28,29]. …”

Effects of Polyphenol-Rich Foods on Human Health

“…Citrus fruit polysaccharides in vitro inhibiting angiogenesis and cell migration [113] Nutrients 2017, 9, 728 [141] jamun fruit NA in vitro inhibiting proliferation and inducing apoptosis [142] cranberry NA in vitro inducing apoptosis and G1 phase arrest [143] Nutrients 2017, 9, 728 [189][190][191] in vitro -inducing cell cycle arrest -lowering the invasive and metastatic potential -stimulating the expression and secretion of IFNγ [192][193][194][195][196][197] red beetroot betanin in vitro showing a dose-dependent cytotoxic effect [198] Nutrients 2017, 9, 728 inhibiting invasion by reducing MMP-9 expression via blockade of NF-κB activation [204] inhibiting invasion by suppressing invadopodium formation and MMP activity [205] inhibiting growth and sustainability of spheroid generated from adherent breast cancer cells [206] ginger 6-dehydrogingerdione in vitro inducing apoptosis and cell cycle arrest in G 2 /M phase [207] garlic diallyl disulfide in vitro inducing apoptosis though: -inhibition of histone deacetylation -inhibition of ERK and the activation of the SAPK/JNK and p38 pathways [216,217] in vitro and in vivo inhibit proliferation and metastasis via: -suppression of the SRC/Ras/ERK pathway -inactivation of the β-catenin signaling pathway [218,219] garlic diallyl trisulfide in vitro and in vivo inducing apoptosis though: -overproduction of ROS and subsequent activation of JNK and AP-1 -upregulating FAS, Bax and p53, and down-regulating Akt and Bcl-2 [220,221] in vitro -inhibiting migration and invasion; -inhibiting ER-α -decreasing protein level of FoxQ1 [213,222,223] garlic S-allyl mercaptocysteine in vitro inducing mitochondrial apoptosis and cell cycle arrest [214] garlic allicin in vitro inhibiting invasion and metastasis [215] black cumin extracts in vitro inducing apoptosis and inhibiting metastasis [224,225] black cumin thymoquinone in vitro and in vivo inducing apoptosis through: -inhibiting Akt phosphorylation -inducing p38 phosphorylation via ROS generation …”