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Abstract Title:

Cucurbitacin B inhibits gastric cancer progression by suppressing STAT3 activity.

Abstract Source:

Arch Biochem Biophys. 2020 Feb 20:108314. Epub 2020 Feb 20. PMID: 32088220

Abstract Author(s):

Jiaxin Xu, Shusheng Yang, Tong Zhou, Yuan Si, Yuchen Xiang, Wei Ke, Te Zhang, Xuewen Liu, Liang Zhang, Ke Xiang, Xinyi Zhang, Huzi Zhao, Ying Liu

Article Affiliation:

Jiaxin Xu

Abstract:

Signal transducer and activator of transcription 3 (STAT3) is expressed aberrantly in multiple tumors, including gastric cancer (GC). STAT3 overexpression and excessive activation have been confirmed to play vital roles in tumorigenesis. Cucurbitacin B (CuB) is a natural product with potent anti-cancer activities in solid tumors. Here, we systematically studied the underlying molecular mechanisms of CuB inhibition of GC both in vitro and in vivo. In GC cell lines, nanomolar concentrations of CuB decreased the phosphorylation of TYR-705 in STAT3 and suppressed STAT3 target gene expression, including c-Myc and Bcl-xL. Computational docking analysis showed that CuB interacts with the DNA-binding domain of STAT3 at several hydrophobic residues. In addition, pull-down experiments showed that CuB is a direct inhibitor of STAT3. CuB in combination with the conventional chemotherapy drug cisplatin exerted enhanced cytotoxicity in GC cells, possibly due to the potentiated inhibition of STAT3 activation. Moreover, a xenograft mouse model confirmed the therapeutic effect of CuB in vivo. These characteristics render CuB a promising candidate drug for further development in the design of new effective STAT3 inhibitors for treating GC.

Study Type : Animal Study, In Vitro Study

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