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Naunyn Schmiedebergs Arch Pharmacol. 2019 Feb 6. doi: 10.1007/s00210-019-01614-5. [Epub ahead of print]

Demethylzeylasteral (T-96) inhibits triple-negative breast cancer invasion by blocking the canonical and non-canonical TGF-β signaling pathways.

Li L1, Ji Y1, Fan J2, Li F3, Li Y3, Wu M4,5, Cheng H6,7, Xu C8,9.

Author information

1
The First Clinical Medical College, Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
2
School of Pharmacy, Nanjing Medical University, Nanjing, 210023, China.
3
Department of Nephrology, Xinqiao Hospital, Army Medical University, Chongqing, 400037, China.
4
The First Clinical Medical College, Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, 210023, China. wumianhuanjucm@163.com.
5
The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China. wumianhuanjucm@163.com.
6
The First Clinical Medical College, Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, 210023, China. nzychb@hotmail.com.
7
The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China. nzychb@hotmail.com.
8
The First Clinical Medical College, Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, 210023, China. cl.xu81@gmail.com.
9
The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China. cl.xu81@gmail.com.

Abstract

Inflammation is one of the characteristic features during the development of human tumors. A pro-inflammatory cytokine that is known to promote inflammation during cancer development is the transforming growth factor-β (TGF-β). On the other hand, demethylzeylasteral (T-96) is a natural compound isolated from Tripterygium wilfordii Hook F, which has been reported to have various pharmacological properties including anti-inflammatory and immunosuppressive activities. We investigated the effects of T-96 on the highly metastatic breast cancer cell line, MDA-MB-231. Cell migration was assessed by scratch-wound migration assay, and the molecular mechanisms underlying the effects of T-96 were examined by qPCR and Western blot analyses. We also investigated the suppression effects of T-96 on the pulmonary metastasis in the 4T1 mouse model. T-96 inhibited TGF-β-induced migration and epithelial-mesenchymal transition both in vitro and in vivo. These results demonstrate that T-96 inhibited invasion of MDA-MB-231 and 4T1 cells via suppressing the canonical and non-canonical TGF-β signaling pathways.

KEYWORDS:

Breast cancer; Invasion; T-96; TGF-β

PMID:
30729271
DOI:
10.1007/s00210-019-01614-5

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