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

• Published in: PloS one 2015-04, Vol.10 (4), p.e0123781-e0123781
• Main Authors: Liu, Yuping, Zhu, Pingting, Wang, Yingyu, Wei, Zhonghong, Tao, Li, Zhu, Zhijie, Sheng, Xiaobo, Wang, Siliang, Ruan, Junshan, Liu, Zhaoguo, Cao, Yuzhu, Shan, Yunlong, Sun, Lihua, Wang, Aiyun, Chen, Wenxing, Lu, Yin
• Format: Article
• Language: English
• Subjects: Allium; Allyl Compounds - chemistry; Allyl Compounds - pharmacology; Animals; Anticancer properties; Apoptosis; Blockage; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer; Cell adhesion & migration; Cell cycle; Cell Line, Tumor; Cell Movement - drug effects; Chinese medicine; Collaboration; Drug Screening Assays, Antitumor; Extracellular matrix; Female; Garlic; Humans; JNK protein; Kinases; MAP Kinase Signaling System - drug effects; Matrix Metalloproteinase 2 - biosynthesis; Matrix Metalloproteinase 9 - biosynthesis; Metastasis; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Proteins - metabolism; NF-kappa B - metabolism; Pharmacy; Prevention; Prostate cancer; Proteins; Signal transduction; Signaling; Sulfides - chemistry; Sulfides - pharmacology; Sulfur; Tumors; Zebrafish
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0123781

Migration 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. MDA-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. DATS 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.