Carnosine retards tumor growth in vivo in an NIH3T3-HER2/neu mouse model
Christof Renner1, Nadine Zemitzsch, Beate Fuchs
1Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Leipzig und Medizinische Fakultät der Universität Leipzig, Leipzig, Germany.
Background:
It was previously demonstrated that the dipeptide carnosine inhibits growth of cultured cells isolated from patients with malignant glioma. In the present work we investigated whether carnosine also affects tumor growth in vivo and may therefore be considered for human cancer therapy.
Results:
A mouse model was used to investigate whether tumor growth in vivo can be inhibited by carnosine. Therefore, NIH3T3 fibroblasts, conditionally expressing the human epidermal growth factor receptor 2 (HER2/neu), were implanted into the dorsal skin of nude mice, and tumor growth in treated animals was compared to control mice. In two independent experiments nude mice that received tumor cells received a daily intra peritoneal injection of 500 microl of 1 M carnosine solution. Measurable tumors were detected 12 days after injection. Aggressive tumor growth in control animals, that received a daily intra peritoneal injection of NaCl solution started at day 16 whereas aggressive growth in mice treated with carnosine was delayed, starting around day 19. A significant effect of carnosine on tumor growth was observed up to day 24. Although carnosine was not able to completely prevent tumor growth, a microscopic examination of tumors revealed that those from carnosine treated animals had a significant lower number of mitosis (p < 0.0003) than untreated animals, confirming that carnosine affects proliferation in vivo.
Conclusion:
As a naturally occurring substance with a high potential to inhibit growth of malignant cells in vivo, carnosine should be considered as a potential anti-cancer drug. Further experiments should be performed in order to understand how carnosine acts at the molecular level.
Insights
The dipeptide carnosine demonstrated anti-cancer properties by inhibiting malignant glioma cell growth in vitro. In vivo studies showed carnosine delays aggressive tumor growth in mice, suggesting its potential as an anti-cancer drug.
Area of Science:
- Oncology
- Biochemistry
Background:
- Carnosine, a dipeptide, previously showed inhibition of malignant glioma cell growth in vitro.
- This study investigates carnosine's efficacy against tumor growth in vivo.
Purpose of the Study:
- To evaluate the anti-cancer potential of carnosine in a mouse model.
- To determine if carnosine affects tumor proliferation in vivo.
Main Methods:
- A mouse model using NIH3T3 fibroblasts expressing HER2/neu was employed.
- Tumor-bearing mice received daily intraperitoneal injections of carnosine solution or NaCl control.
- Tumor growth and proliferation rates (mitosis) were monitored and compared.
Main Results:
- Carnosine treatment delayed the onset of aggressive tumor growth from day 16 to day 19.
- A significant inhibitory effect on tumor growth was observed up to day 24.
- Microscopic analysis revealed a significantly lower number of mitoses in tumors from carnosine-treated mice (p < 0.0003).
Conclusions:
- Carnosine exhibits potential as an anti-cancer agent due to its in vivo tumor growth inhibition.
- Further research is warranted to elucidate the molecular mechanisms of carnosine's anti-cancer action.
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