Butein promotes ubiquitination-mediated survivin degradation inhibits tumor growth and overcomes chemoresistance

Author:

Dong Xin,Liu Wenbin,Li Xiaoying,Gan Yu,Zhou Li,Li Wei,Xie Li

Abstract

AbstractOverexpression of survivin is frequently observed in human malignancies and is associated with poor prognosis. The present study found that survivin is highly expressed in nasopharyngeal carcinoma (NPC) tumor tissues. Depleting survivin with shRNA inhibited cell viability, colony formation, and in vivo tumorigenesis of NPC cells. With a natural product screening, we identified Butein as a potential anti-tumor compound for NPC by reducing survivin protein level. Butein shortened the half-life of survivin and enhanced ubiquitination-mediated degradation. The mechanism study showed that Butein promoted the interaction between survivin and E3 ligase Fbxl7, and the knockdown of Fbxl7 compromised Butein-induced survivin ubiquitination. Butein suppressed the Akt-Wee1-CDK1 signaling and decreased survivin Thr34 phosphorylation, facilitating E3 ligase Fbxl7-mediated survivin ubiquitination and degradation. Moreover, Butein exhibited a strong in vivo anti-tumor activity, as the tumor volume of Butein-treated xenografts was reduced significantly. Butein alone or combined with cisplatin (CDDP) overcame chemoresistance in NPC xenograft tumors. Overall, our data indicate that Butein is a promising anti-tumor agent for NPC treatment.

Funder

Scientific Research Program of Hunan Provincial Health Committee

National Natural Science Foundation of China

Natural Science Foundation of Hunan Province

Natural Science Foundation of Hunan Province

Basic Research Project of Changsha Science and Technology Bureau

Scientific Research Program of Hunan Provincial Health Committee

Climbing plan of Hunan Cancer Hospital

Publisher

Springer Science and Business Media LLC

Subject

Multidisciplinary

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