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Antitumor activity of apoptotic nuclease TBN1 from L. esculentum
J Matousek1, T Podzimek, P Pouckova
1Biology Centre, Academy of Sciences of the Czech Republic v.v.i., Institute of Plant Molecular Biology, Czech Republic.
Abstract:
Nuclease from tomato (TBN1) was produced by in planta biotechnology purified and tested for its anticarcinogenic properties. The nuclease was cytostatic after its intratumoral administration to nude mice bearing human melanoma or prostate carcinoma or after tumor targeting by TBN1 administration intravenously as conjugate with polyethylene glycol (PEG). Inhibitory effects of TBN1 on tumor growth were comparable to effects of bovine seminal RNase (BS-RNase), but the inhibition was reached at about ten times lower protein concentration. Simultaneously, TBN1 exhibited a lower degree of embryotoxicity compared to BS-RNAse and other nucleases. TBN1 showed significant stability in vivo, because it was readily detected after its administration intratumorally or intravenously by the fluorescence methods. Intravenous administration of TBN1-PEG caused significant inhibition of tumor proliferation without obvious degenerative changes, while direct administration of TBN1 into melanoma tumors led to rapid tumor tissue degeneration. The fact can be essential for the mode of TBN1 biological action that mature nuclease is a small (36 kDa) thermostable glycoprotein that has ability to destroy human 28S, 18S, 7S and 5.8S RNA, circular RNAs, double-stranded RNA in vitro and shows DNase and 3'nucleotidase activities.
Insights
Tomato nuclease (TBN1) exhibits potent anticarcinogenic properties, effectively inhibiting tumor growth in mice. This novel nuclease demonstrates comparable efficacy to existing treatments but at lower concentrations and with reduced toxicity.
Area of Science:
- Biotechnology
- Oncology
- Enzymology
Background:
- Anticancer therapies often face challenges with efficacy and toxicity.
- Nucleases are enzymes with potential therapeutic applications due to their ability to degrade nucleic acids.
Purpose of the Study:
- To produce and characterize a novel nuclease from tomato (TBN1) for its anticarcinogenic potential.
- To evaluate the efficacy and safety of TBN1 in preclinical cancer models.
Main Methods:
- Production of TBN1 using in planta biotechnology.
- Administration of TBN1 intratumorally and intravenously (as TBN1-PEG conjugate) in mice bearing human melanoma or prostate carcinoma.
- Assessment of tumor growth inhibition, cytotoxicity, embryotoxicity, and in vivo stability using fluorescence methods.
Main Results:
- TBN1 demonstrated significant cytostatic effects on melanoma and prostate carcinoma xenografts.
- Tumor growth inhibition by TBN1 was comparable to bovine seminal RNase (BS-RNase) but at a ten-fold lower protein concentration.
- TBN1 exhibited lower embryotoxicity than BS-RNase and other nucleases, with good in vivo stability.
- Intravenous TBN1-PEG administration inhibited tumor proliferation without significant degenerative changes, while direct TBN1 administration caused rapid tumor tissue degeneration.
Conclusions:
- Tomato nuclease (TBN1) is a promising candidate for cancer therapy due to its potent anticarcinogenic activity, favorable safety profile, and stability.
- TBN1's mechanism may involve RNA degradation, as it effectively degrades various RNA types in vitro.
- Further research into TBN1's therapeutic potential and mechanism of action is warranted.
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01:31The Intrinsic Apoptotic Pathway
01:17The Extrinsic Apoptotic Pathway