Carnosine retards tumor growth in vivo in an NIH3T3-HER2/neu mouse model.
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.


CONCLUSIONS
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.
Renner
Christof
C
Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Leipzig und Medizinische Fakultät der Universität Leipzig, Leipzig, Germany.
Zemitzsch
Nadine
N
Fuchs
Beate
B
Geiger
Kathrin D
KD
Hermes
Matthias
M
Hengstler
Jan
J
Gebhardt
Rolf
R
Meixensberger
Jürgen
J
Gaunitz
Frank
F
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002336:Carnosine / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004354:Drug Screening Assays, Antitumor; D005260:Female; D007274:Injections, Intraperitoneal; D051379:Mice; D008819:Mice, Nude; D008938:Mitosis / Q000187:drug effects; D041681:NIH 3T3 Cells; D009369:Neoplasms / Q000473:pathology*; D010088:Oxidoreductases / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*
D000255:Adenosine Triphosphate; D002336:Carnosine; D010088:Oxidoreductases; D018719:Erb-b2 Receptor Tyrosine Kinases; C524056:Erbb2 protein, mouse