Structural analysis of toxic volkensin, a type 2 ribosome inactivating protein from Adenia volkensii Harm (kilyambiti plant): Molecular modeling and surface analysis by computational methods and limited proteolysis

Severino, Valeria; Paiardini, Alessandro; Pascarella, Stefano; Parente, Augusto

doi:10.1016/j.ijbiomac.2009.06.015

Cited by 3 publications

(3 citation statements)

References 42 publications

(46 reference statements)

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“…This technique allows mass quantities of fordin to be obtained for further biological activity investigations and application. The results of the enzyme activity assay showed that fordin had N-glycosidase activity which may lead to ribosome inactivation, as with the majority of the reported RIPs from different plant species ( 32 ).…”

Section: Discussionmentioning

confidence: 53%

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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

Mao

Chen

et al. 2018

Int J Oncol

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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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Section: Discussionmentioning

confidence: 53%

“…The fordin amino acid residues, Tyr-109 (Y), Tyr-148 (Y), Glu-197 (E), Arg-200 (R), and Trp-229 (W), aligned perfectly with the consensus active site sequences of RIPs ( Fig. 1 ) ( 32 ).…”

Section: Resultsmentioning

confidence: 71%

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

Mao

Chen

et al. 2018

Int J Oncol

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“…Modeccin and volkensin, from Adenia (Modecca) digitata (Harv.) Engl and Adenia volkensii Harms, respectively, were the first type 2 RIPs purified and characterized from Adenia plants [ 20 , 21 , 22 , 23 , 24 , 25 ]. Moreover, three highly cytotoxic type 2 RIPs from Adenia lanceolata Engl., Adenia stenodactyla Harms, and Adenia kirkii (Mast) Engl.…”

Section: Introductionmentioning

confidence: 99%

Heterophyllin: A New Adenia Toxic Lectin with Peculiar Biological Properties

Bortolotti,

Biscotti,

Zanello

et al. 2023

Toxins

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Ribosome-inactivating proteins (RIPs) are plant toxins that were identified for their ability to irreversibly damage ribosomes, thereby causing arrest of protein synthesis and induction of cell death. The RIPs purified from Adenia plants are the most potent ones. Here, we describe a novel toxic lectin from Adenia heterophylla caudex, which has been named heterophyllin. Heterophyllin shows the enzymatic and lectin properties of type 2 RIPs. Interestingly, in immunoreactivity experiments, heterophyllin poorly cross-reacts with sera against all other tested RIPs. The cytotoxic effects and death pathways triggered by heterophyllin were investigated in three human-derived cell lines: NB100, T24, and MCF7, and compared to ricin, the most known and studied type 2 RIP. Heterophyllin was able to completely abolish cell viability at nM concentration. A strong induction of apoptosis, but not necrosis, and the involvement of oxidative stress and necroptosis were observed in all the tested cell lines. Therefore, the enzymatic, immunological, and biological activities of heterophyllin make it an interesting molecule, worthy of further in-depth analysis to verify its possible pharmacological application.

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Ribosome inactivating proteins – An unfathomed biomolecule for developing multi-stress tolerant transgenic plants

Mishra

Shamra

2022

International Journal of Biological Macromolecules

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Structural analysis of toxic volkensin, a type 2 ribosome inactivating protein from Adenia volkensii Harm (kilyambiti plant): Molecular modeling and surface analysis by computational methods and limited proteolysis

Cited by 3 publications

References 42 publications

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

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

Heterophyllin: A New Adenia Toxic Lectin with Peculiar Biological Properties

Ribosome inactivating proteins – An unfathomed biomolecule for developing multi-stress tolerant transgenic plants

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