Supramolecular Organization As a Factor of Ribonuclease Cytotoxicity
E V Dudkina1, V V Ulyanova1, O N Ilinskaya1
1Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, Kazan, 420008 Russia.
Abstract:
One of the approaches used to eliminate tumor cells is directed destruction/modification of their RNA molecules. In this regard, ribonucleases (RNases) possess a therapeutic potential that remains largely unexplored. It is believed that the biological effects of secreted RNases, namely their antitumor and antiviral properties, derive from their catalytic activity. However, a number of recent studies have challenged the notion that the activity of RNases in the manifestation of selective cytotoxicity towards cancer cells is exclusively an enzymatic one. In this review, we have analyzed available data on the cytotoxic effects of secreted RNases, which are not associated with their catalytic activity, and we have provided evidence that the most important factor in the selective apoptosis-inducing action of RNases is the structural organization of these enzymes, which determines how they interact with cell components. The new idea on the preponderant role of non-catalytic interactions between RNases and cancer cells in the manifestation of selective cytotoxicity will contribute to the development of antitumor RNase-based drugs.
Insights
Secreted ribonucleases (RNases) show promise for cancer therapy. Their antitumor effects may stem from structural interactions with cancer cells, not just enzymatic activity, paving the way for novel drug development.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Therapeutics
Background:
- Targeting tumor cell RNA is a strategy for cancer treatment.
- Secreted ribonucleases (RNases) have largely unexplored therapeutic potential.
- The antitumor and antiviral effects of RNases are traditionally attributed to their catalytic activity.
Purpose of the Study:
- To review the cytotoxic effects of secreted RNases beyond their catalytic activity.
- To investigate the role of RNase structure in selective cancer cell cytotoxicity.
- To propose a new therapeutic strategy for RNase-based antitumor drugs.
Main Methods:
- Literature review of studies on secreted RNases and cancer cells.
- Analysis of data on non-catalytic cytotoxic effects of RNases.
- Evaluation of the role of enzyme structure in cell component interaction.
Main Results:
- Recent studies challenge the exclusive role of enzymatic activity in RNase-induced cancer cell cytotoxicity.
- The structural organization of RNases is crucial for their selective apoptosis-inducing action.
- Non-catalytic interactions between RNases and cancer cells significantly contribute to selective cytotoxicity.
Conclusions:
- The therapeutic potential of RNases in cancer treatment is significant.
- Non-catalytic interactions, driven by RNase structure, are key to selective cytotoxicity.
- This understanding can guide the development of novel, structure-based RNase antitumor drugs.
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