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Abstract Title:

Isoorientin inhibits epithelial-to-mesenchymal properties and cancer stem-cell-like features in oral squamous cell carcinoma by blocking Wnt/β-catenin/STAT3 axis.

Abstract Source:

Toxicol Appl Pharmacol. 2021 08 1 ;424:115581. Epub 2021 May 18. PMID: 34019859

Abstract Author(s):

Shao-Cheng Liu, Chin-Sheng Huang, Chih-Ming Huang, Ming-Shou Hsieh, Mao-Suan Huang, Iat-Hang Fong, Chi-Tai Yeh, Chih-Cheng Lin

Article Affiliation:

Shao-Cheng Liu

Abstract:

Oral squamous cell carcinoma (OSCC) is among the most prevalent cancers of the head and neck. This study revealed that isoorientin attenuates OSCC cell stemness and epithelial-mesenchymal transition potential through the inhibition of JAK/signal transducer and activator of transcription 3 (STAT3) and Wnt/β-catenin signaling in cell lines. Our findings indicated that isoorientin is a potential inhibitor of β-catenin/STAT3 in vitro and in vivo. We analyzed possible synergism between isoorientin and cisplatin in OSCC. A sulforhodamine B assay, colony formation assay, tumorsphere-formation assay, andWnt reporter activity assay were used for determining cell invasion, cell migration, drug cytotoxicity, and cell viability with potential molecular mechanisms in vitro. Isoorientin reduced the expression of p-STAT3, β-catenin, and p-GSK3 as well as downstream effectors TCF1/TCF7 and LEF1 and significantly reduced β-catenin colocalization in the nucleus. Isoorientin markedly strengthened the cytotoxic effects of cisplatin against SAS and SCC-25. Therefore, combining isoorientin and cisplatin treatments can potentially improve the anticancer effect of cisplatin. Isoorientin inhibited the tumorigenicity and growth of OSCC through the abrogation of Wnt/β-catenin/STAT3 signaling in vivo. Thus, isoorientin disrupted the β-catenin signaling pathway through the inactivation of STAT3 signaling. In conclusion, targeting OSCC-SC-mediated stemness with isoorientin to eradicate OSCC-SCs may be aneffective strategy for preventing relapse and metastasis of OSCC and providing long-term survival benefits.

Study Type : In Vitro Study

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