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.
BACKGROUND
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.


RESULTS
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.


CONCLUSIONS
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.
School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
Yuping
Y
Liu
School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China; Medical College of Yangzhou University, Yangzhou, China.
Pingting
P
Zhu
School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
Yingyu
Y
Wang
School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
Zhonghong
Z
Wei
School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
Li
L
Tao
School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
Zhijie
Z
Zhu
School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
Xiaobo
X
Sheng
School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
Siliang
S
Wang
School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
Junshan
J
Ruan
School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
Zhaoguo
Z
Liu
School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
Yuzhu
Y
Cao
School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
Yunlong
Y
Shan
School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
Lihua
L
Sun
School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China; Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine (TCM) Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
Aiyun
A
Wang
School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China; Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine (TCM) Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
Wenxing
W
Chen
School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China; Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine (TCM) Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
Yin
Y
Lu
D000498:Allyl Compounds / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000378:metabolism*; D013440:Sulfides / Q000737:chemistry / Q000494:pharmacology*; D015027:Zebrafish
D000498:Allyl Compounds; D016328:NF-kappa B; D009363:Neoplasm Proteins; D013440:Sulfides; C042577:diallyl trisulfide; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9