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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.
- Source :
-
International journal of oncology [Int J Oncol] 2018 Sep; Vol. 53 (3), pp. 1027-1042. Date of Electronic Publication: 2018 Jul 04. - Publication Year :
- 2018
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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.
- Subjects :
- Apoptosis drug effects
Cell Line, Tumor
Cell Movement drug effects
Cell Survival drug effects
Down-Regulation
Drug Screening Assays, Antitumor
Gene Expression Regulation, Neoplastic drug effects
Humans
I-kappa B Kinase metabolism
Inhibitory Concentration 50
Matrix Metalloproteinase 9 metabolism
Minor Histocompatibility Antigens metabolism
NF-kappa B metabolism
Neoplasm Invasiveness prevention & control
Neoplasms pathology
Phosphorylation drug effects
Plant Proteins isolation & purification
Plant Proteins therapeutic use
Proto-Oncogene Proteins c-bcl-2 metabolism
RNA, Messenger metabolism
RNA, Small Interfering metabolism
Recombinant Proteins isolation & purification
Recombinant Proteins pharmacology
Recombinant Proteins therapeutic use
Ribosome Inactivating Proteins therapeutic use
Up-Regulation
Euphorbiaceae metabolism
Neoplasms drug therapy
Plant Proteins pharmacology
Ribosome Inactivating Proteins pharmacology
Signal Transduction drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1791-2423
- Volume :
- 53
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- International journal of oncology
- Publication Type :
- Academic Journal
- Accession number :
- 30015835
- Full Text :
- https://doi.org/10.3892/ijo.2018.4470