Journal
BIOCHEMICAL PHARMACOLOGY
Volume 206, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bcp.2022.115299
Keywords
Triple negative breast cancer (TNBC); Epithelial-mesenchymal transition (EMT); Proliferation; Sesamol; Wnt/beta-catenin signaling
Categories
Funding
- Zhejiang Provincial Natural Science Foundation of China [LQ20H260010]
- Young and Middle-aged Scientific Research Startup Fund of Zhejiang University School of Medicine-Affiliated Jinhua Hospital in China [JY2018-1-02]
- Jinhua Municipal Science and Technology Research Project of Zhejiang Province in China [2019-4-006]
- Medical Health Science and Technology Project of Zhejiang Provincial Health Commission in China [2020KY1003]
Ask authors/readers for more resources
Sesamol inhibits proliferation, migration, and invasion of triple negative breast cancer (TNBC) cells by attenuating PCNA, CyclinD1 expression and reverting epithelial-mesenchymal transition (EMT). It also inactivates the Wnt/beta-catenin signaling pathway and induces the expression of Wnt inhibitory factor 1 (WIF1), which leads to the inhibition of TNBC growth and metastasis.
Triple negative breast cancer (TNBC), a particularly aggressive breast cancer subtype without estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor 2 (HER2) expression, possesses highly invasive capacity, uncontrolled proliferative phenotype and poor clinical prognosis. Sesamol enriched in sesame seeds has been widely reported as a metabolic modulator due to its anti-aging, anti-hepatotoxic and cardio-protective properties. In this study, we found that sesamol significantly inhibited proliferation, migration and invasion of TNBC cells via attenuating PCNA, CyclinD1 expression and reversion of epithelial-mesenchymal transition (EMT) characterized by increased epithelial marker E-cadherin and decreased mesenchymal marker N-cadherin, Vimentin, Snail expression. Moreover, sesamol inactivated Wnt/beta-catenin signaling and Wnt agonist 1 AMBMP application reversed the inhibition of proliferation, migration and invasion of TNBC by sesamol administration. Subsequently, our data showed that sesamol induced Wnt inhibitory factor 1 (WIF1), an endogenous inhibitor of Wnt/beta-catenin pathway, expression and WIF1 artificial knockdown abrogated the inactivation of Wnt/beta-catenin signaling by sesamol exposure in TNBC cells. And we found that promoter region de-methylation was responsible for WIF1 up-regulation by sesamol administration. Finally, with the xenograft assay using nude mice, we also found that sesamol inhibited proliferation and metastasis of TNBC via WIF1-induced inactivation of Wnt/beta-catenin signaling in vivo. Collectively, these data added novel understandings and evidences to the anti-cancer properties of sesamol.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available