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A novel class of peptides that induce apoptosis and abrogate tumorigenesis in vivo
M Resnicoff1, Z Huang, D Herbert
1Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. resnicol@jeflin.tju.edu
Abstract:
In testing the ability of certain synthetic peptides of biological origin to bind to cell surfaces, we unexpectedly found that they could induce apoptosis and inhibit tumorigenesis in rodent and human tumor cell lines. In vitro pre-incubation with the peptides at concentrations as low as 10(-12) M inhibited tumorigenesis in nude mice, in a dose-dependent fashion. The inhibition of tumorigenesis was reflected in the rapid induction of apoptosis of tumor cells, pre-incubated with the peptides, and tested under conditions of anchorage-independence. Induction of apoptosis was detectable even at concentrations of 10(-12)-10(-13) M (0.1-1.0 pM). Aspecific toxicity of the synthetic peptides was ruled out by the demonstration that single amino acid substitutions (in at least 4 peptides) completely abrogated the pro-apoptotic effect, even at a concentration of 10(-5) M (10 microM).
Insights
Synthetic peptides unexpectedly induce apoptosis and inhibit tumor growth in cell lines and animal models. These peptides show potent anti-tumor effects at picomolar concentrations, demonstrating specific biological activity.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Synthetic peptides are being investigated for cell surface binding capabilities.
- Unexpected biological activities of peptides can emerge during research.
Purpose of the Study:
- To investigate the potential of synthetic peptides to induce apoptosis and inhibit tumorigenesis.
- To determine the effective concentrations and specificity of these peptide activities.
Main Methods:
- Testing synthetic peptides for cell surface binding and subsequent effects on tumor cell lines (rodent and human).
- In vitro pre-incubation of tumor cells with peptides, followed by tumorigenesis assays in nude mice.
- Assessing apoptosis induction under anchorage-independent conditions.
- Evaluating specificity through single amino acid substitution mutants.
Main Results:
- Synthetic peptides induced apoptosis and inhibited tumorigenesis in various tumor cell lines.
- Significant inhibition of tumorigenesis in nude mice observed at peptide concentrations as low as 10(-12) M, in a dose-dependent manner.
- Apoptosis induction was detectable at 0.1-1.0 pM concentrations.
- Single amino acid substitutions abolished the pro-apoptotic effect, confirming specificity and ruling out non-specific toxicity.
Conclusions:
- Certain synthetic peptides possess potent pro-apoptotic and anti-tumorigenic properties.
- These peptides demonstrate high efficacy at extremely low (picomolar) concentrations.
- The observed effects are specific to the peptide sequence, indicating a targeted biological mechanism.