Fordin: A novel type I ribosome inactivating protein from Vernicia fordii modulates multiple signaling cascades leading to anti-invasive and pro-apoptotic effects in cancer cells in vitro

Lu,Weili; Mao,Yingji; Chen,Xue; Ni,Jun; Zhang,Rui; Wang,Yuting; Wang,Jun; Wu,Lifang

doi:10.3892/ijo.2018.4470

Fordin: A novel type I ribosome inactivating protein from Vernicia fordii modulates multiple signaling cascades leading to anti-invasive and pro-apoptotic effects in cancer cells in vitro

Authors:
- Weili Lu
- Yingji Mao
- Xue Chen
- Jun Ni
- Rui Zhang
- Yuting Wang
- Jun Wang
- Lifang Wu
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Affiliations: Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui 230031, P.R. China
Published online on: July 4, 2018 https://doi.org/10.3892/ijo.2018.4470
Pages: 1027-1042
Copyright: © Lu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Fordin, which is derived from Vernicia fordii, is a novel type I ribosome inactivating protein (RIP) with RNA N-glycosidase activity. In the present study, fordin was expressed by Escherichia coli and purified using nickel affinity chromatography. Previous studies have demonstrated RIP toxicity in a variety of cancer cell lines. To understand the therapeutic potential of fordin on tumors, the present study investigated the effects of fordin on the viability of several tumor and normal cell lines. The results demonstrated that fordin induced significant cytotoxicity in four cancer cell lines, compared with the normal cell line. Specifically, profound apoptosis and inhibition of cell invasion were observed following fordin exposure in U-2 OS and HepG2 cells; however, the molecular mechanism underlying the action of RIP remains to be fully elucidated. In the present study, it was found that the anticancer effects of fordin were associated with suppression of the nuclear factor (NF)-κB signaling pathway. In U-2 OS and HepG2 cells, fordin inhibited the expression of inhibitor of NF-κB (IκB) kinase, leading to downregulation of the phosphorylation level of IκB, which quelled the nuclear translocation of NF-κB. Fordin also reduced the mRNA and protein levels of NF-κB downstream targets associated with cell apoptosis and metastasis, particularly B-cell lymphoma‑2-related protein A1 (Blf-1) and matrix metalloproteinase (MMP)-9. The inactivation of NF-κB and the reduction in the expression levels of Blf-1 and MMP-9 mediated by fordin were also confirmed by co-treatment with lipopolysaccharide or p65 small interfering RNA. These findings suggested a possible mechanism for the fordin-induced effect on tumor cell death and metastasis. The results of the present study demonstrated the multiple anticancer effects of fordin in U-2 OS and HepG2 cells, in part by inhibiting activation of the NF-κB signaling pathway.

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