Demethylzelasteral inhibits proliferation and EMT via repressing Wnt/β-catenin signaling in esophageal squamous cell carcinoma

Abstract

As a kind of tumor commonly seen, no effective treatment is available for esophageal squamous cell carcinoma (ESCC). Therefore, seeking a new treatment is urgent. Demethylzeylasteral (T-96) isolated from Tripterygium wilfordii root bark embraces outstanding good antitumor activity. However, as for the mechanism of T-96 work on ESCC cells, it is rarely reported. In this study, we found that T-96 has inhibition when ESCC cells are proliferating, migrating and cloning. Moreover, relevant effects are influenced by dose and time. And T-96 can result in the stop of G2/M phase and induce apoptosis of ESCC cells. In addition, the expressions of Cyclin B1, Cyclin D1, Bcl-2, PARP1 and Survivin were decreased after starch demethylation. Despite of this, Bax and PARP1's expressions went up. To add up, there was an obvious increase in the expression of E-cadherin, while that of N-cadherin, Vimentin and MMP9 decreased after T-96 treatment. Moreover, the expression of Wnt/β-Catenin pathway, which concerns proteins β-Catenin, c-Myc and Wnt3a decreased. Our study shows that T-96 inhibits the proliferation and migration of esophageal cancer cells through Wnt/β-catenin pathway. Moreover, it gives rise to cell cycle arrest and apoptosis. According to the research results, T-96 tends to be put into use when treating ESCC patients, thus laying the experimental foundation for clinical research.

Molecular subtyping of esophageal squamous cell carcinoma by large-scale transcriptional profiling: Characterization, therapeutic targets, and prognostic value

“…Besides, Wnt signaling was reported to be inversely correlated with T cell infiltration in colorectal cancer, ( Grasso et al, 2018 ), as we also found a lower T cell infiltration in subtype 1 than in other subtypes. The Wnt signaling pathway activation is associated with tumorigenesis and progression ( Nusse and Varmus, 1992 ; Zhan et al, 2017 ; You et al, 2019 ); tumor proliferation and progression were inhibited by suppressing this pathway ( Lee et al, 2012 ; You et al, 2019 ; Yu et al, 2021 ).…”

Pharmacological inhibition of demethylzeylasteral on JAK-STAT signaling ameliorates vitiligo

“…Furthermore, T-96 could reduce immunocompetent cells and inflammatory mediators in the rabbit model of atherosclerosis [ 19 ], inhibit inflammatory responses in mice with lupus nephritis [ 20 – 22 ], and suppress RNA-dependent RNA polymerase of hepatitis C virus [ 23 ]. Additionally, T-96 demonstrates anti-cancer abilities by inhibiting angiogenesis, cell proliferation, and cell apoptosis [ 15 , 24 – 27 ]. Accumulating evidence suggests that T-96 may have the potential to be used in COVID-19 [ 28 ], arthritis [ 22 ], and other autoimmune disorders [ 22 , 28 ] as a novel therapeutic agent.…”