Oncotarget

Research Papers:

Cooperative down-regulation of ribosomal protein L10 and NF-κB signaling pathway is responsible for the anti-proliferative effects by DMAPT in pancreatic cancer cells

Chen Shi, Yang Wang, Yuna Guo, Yijun Chen _ and Nan Liu

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Oncotarget. 2017; 8:35009-35018. https://doi.org/10.18632/oncotarget.16557

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Abstract

Chen Shi1,*, Yang Wang1,*, Yuna Guo1, Yijun Chen1 and Nan Liu1

1State Key Laboratory of Natural Medicines and Laboratory of Chemical Biology, China Pharmaceutical University, Nanjing, Jiangsu Province, 210009, People’s Republic of China

*These authors have contributed equally to this work

Correspondence to:

Yijun Chen, email: yjchen@cpu.edu.cn

Nan Liu, email: liunan@cpu.edu.cn

Keywords: DMAPT, RPL10, NF-κB pathway, mechanism, pancreatic cancer

Received: September 26, 2016     Accepted: March 09, 2017     Published: March 25, 2017

ABSTRACT

Dimethylaminoparthenolide (DMAPT), a water-soluble analogue of natural product parthenolide, possesses anti-inflammatory and anti-tumor activities. Despite that the anti-inflammatory mechanism of DMAPT has been well studied, specific target(s) for DMPAT and its anti-tumor mechanism remain poorly understood. In this study, to assess the anti-proliferative effects of DMAPT in pancreatic cancer cell lines and exploit its anti-tumor mechanism, serial affinity chromatograph was implemented to probe potential targets for DMAPT, revealing that ribosomal protein L10 (RPL10) is a specific binding protein of DMAPT in PANC-1 cells. DMAPT could decrease the expression of RPL10 accompanying its anti-proliferative effects. Mechanistically, in both PANC-1 cells and MiaPaca-2 cells, reduced expression of RPL10 triggered by DMAPT binding decreased the expression of either p65 or IKKγ through the direct binding between RPL10 and p65 or IKKγ. Together, the present study strongly implies that RPL10 is a novel target with therapeutic potential for the treatment of pancreatic cancer.


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