Bacillus pumilus Ribonuclease Inhibits Migration of Human Duodenum Adenocarcinoma HuTu 80 Cells

Zelenikhin, P. V.; Mohamed, Islam S.; Nadyrova, Alsu; Sirotkina, A. A.; Ulyanova, Vera; Миронова, Н. Л.; Mitkevich, Vladimir A.; Makarov, Alexander А.; Зенкова, М. А.; Ilinskaya, О. N.

doi:10.1134/s0026893320010173

Cited by 8 publications

(3 citation statements)

References 17 publications

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“…Additionally, the significant associations of target genes with inflammation, virus reproduction ("Hepatitis C" and "Hepatitis B") and cell adhesion were in good agreement with the previously reported activities of binase, including its stimulating effect on M1 macrophage polarisation [56] and the expression of TNF and NF-κB-related genes in leukemic Kasumi-1 cells [23]. Moreover, binase has inhibitory effects on the replication of RNA viruses [30,34] and the motility of tumour cells [57].…”

Section: Discussionsupporting

confidence: 87%

Antitumour Activity of the Ribonuclease Binase from Bacillus pumilus in the RLS40 Tumour Model Is Associated with the Reorganisation of the miRNA Network and Reversion of Cancer-Related Cascades to Normal Functioning

et al. 2020

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The important role of miRNA in cell proliferation and differentiation has raised interest in exogenous ribonucleases (RNases) as tools to control tumour-associated intracellular and extracellular miRNAs. In this work, we evaluated the effects of the RNase binase from Bacillus pumilus on small non-coding regulatory RNAs in the context of mouse RLS40 lymphosarcoma inhibition. In vitro binase exhibited cytotoxicity towards RLS40 cells via apoptosis induction through caspase-3/caspase-7 activation and decreased the levels of miR-21a, let-7g, miR-31 and miR-155. Intraperitoneal injections of binase in RLS40-bearing mice resulted in the retardation of primary tumour growth by up to 60% and inhibition of metastasis in the liver by up to 86%, with a decrease in reactive inflammatory infiltration and mitosis in tumour tissue. In the blood serum of binase-treated mice, decreases in the levels of most studied miRNAs were observed, excluding let-7g, while in tumour tissue, the levels of oncomirs miR-21, miR-10b, miR-31 and miR-155, and the oncosuppressor let-7g, were upregulated. Analysis of binase-susceptible miRNAs and their regulatory networks showed that the main modulated events were transcription and translation control, the cell cycle, cell proliferation, adhesion and invasion, apoptosis and autophagy, as well as some other tumour-related cascades, with an impact on the observed antitumour effects.

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Section: Discussionsupporting

confidence: 87%

Antitumour Activity of the Ribonuclease Binase from Bacillus pumilus in the RLS40 Tumour Model Is Associated with the Reorganisation of the miRNA Network and Reversion of Cancer-Related Cascades to Normal Functioning

et al. 2020

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“…As an antitumor agent, we used the bacterial RNase binase from Bacillis pumilus , which previously showed inhibition of the proliferation and migration of intestinal cancer cells [ 55 ]. We previously showed that binase did not act on normal fibroblasts but had a toxic effect on ras-transformed tumor cells [ 6 ].…”

Section: Discussionmentioning

confidence: 99%

Fibrin-Rhamnogalacturonan I Composite Gel for Therapeutic Enzyme Delivery to Intestinal Tumors

Faizullin

Valiullina

Salnikov

et al. 2023

IJMS

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Therapy of colorectal cancer with protein drugs, including targeted therapy using monoclonal antibodies, requires the preservation of the drug’s structure and activity in the gastrointestinal tract or bloodstream. Here, we confirmed experimentally the fundamental possibility of creating composite protein–polysaccharide hydrogels based on non-degrading rhamnogalacturonan I (RG) and fibrin as a delivery vehicle for antitumor RNase binase. The method is based on enzymatic polymerization of fibrin in the presence of RG with the inclusion of liposomes, containing an encapsulated enzyme drug, into the gel network. The proposed method for fabricating a gel matrix does not require the use of cytotoxic chemical cross-linking agents and divalent cations, and contains completely biocompatible and biodegradable components. The process proceeds under physiological conditions, excluding the effect of high temperatures, organic solvents and ultrasound on protein components. Immobilization of therapeutic enzyme binase in the carrier matrix by encapsulating it in liposomes made from uncharged lipid made it possible to achieve its prolonged release with preservation of activity for a long time. The release time of binase from the composite carrier can be regulated by variation of the fibrin and RG concentration.

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“…Previously, we have shown that binase, a cytotoxic ribonuclease from Bacillus pumilus, directly interacts with wildtype KRAS protein in MLE-12 cells, which leads to the inhibition of the MAPK/ERK pathway and induction of apoptosis in tumor cells [14]. Moreover, binase selectively inhibits the growth of tumor cells expressing KIT, AML/ETO, FLT3, E6, and E7 oncogenes [15][16][17] and suppresses the migration of cancer cells [18]. However, the antitumor potential of binase is mediated not only by the interaction with oncogenes but also involves the cationic nature of the enzyme allowing its predominant interaction with the cancer cells' membranes, as well as the suppression of K Ca channels and RNA cleavage [19].…”

Section: Introductionmentioning

confidence: 99%

Two Main Cancer Biomarkers as Molecular Targets of Binase Antitumor Activity

Dudkina,

Ulyanova,

Asmandiyarova

et al. 2024

BioMed Research International

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Cancer is frequently coupled with the disturbance of key signaling pathways. Aberrant activation of the mitogen-activated protein kinase (MAPK) signaling cascade, occurring in over 85% of cancers, is mainly caused by the genetic alterations of its main components—oncogenes EGFR and RAS, and plays a crucial role in cell fate. The importance of EGFR and RAS proteins in a variety of tumors suggests that they would be good therapeutic targets, but at present, no effective targeted therapy against these two oncogenes has been proven. Here, we show that ribonuclease from Bacillus pumilus (binase) inhibits MAPK signaling through direct interaction with EGFR and RAS proteins. This effect contributes to the antitumor potential of binase along with its enzymatic activity. Multitargeticity of binase prevents the development of drug resistance, which is considered a major obstacle to effective anticancer treatment.

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Bacillus pumilus Ribonuclease Inhibits Migration of Human Duodenum Adenocarcinoma HuTu 80 Cells

Cited by 8 publications

References 17 publications

Antitumour Activity of the Ribonuclease Binase from Bacillus pumilus in the RLS40 Tumour Model Is Associated with the Reorganisation of the miRNA Network and Reversion of Cancer-Related Cascades to Normal Functioning

Antitumour Activity of the Ribonuclease Binase from Bacillus pumilus in the RLS40 Tumour Model Is Associated with the Reorganisation of the miRNA Network and Reversion of Cancer-Related Cascades to Normal Functioning

Fibrin-Rhamnogalacturonan I Composite Gel for Therapeutic Enzyme Delivery to Intestinal Tumors

Two Main Cancer Biomarkers as Molecular Targets of Binase Antitumor Activity

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