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

Renner C, Zemitzsch N, Fuchs B, Geiger KD, Hermes M, Hengstler J, Gebhardt R, Meixensberger J, Gaunitz F - Mol. Cancer (2010)

Bottom Line: A significant effect of carnosine on tumor growth was observed up to day 24.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Leipzig und Medizinische Fakultät der Universität Leipzig, Leipzig, Germany.

ABSTRACT

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.

Show MeSH

Related in: MedlinePlus

Microscopic images from tumors stained with Hematoxylin-Eosin from an animal treated with carnosine (right) and from a control animal treated with NaCl solution (left). Many mitotic figures are seen in the tumor from the non-treated animal compared to the tumor from the treated animal. Pictures were taken at an original magnification of 400×.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2818694&req=5

Figure 3: Microscopic images from tumors stained with Hematoxylin-Eosin from an animal treated with carnosine (right) and from a control animal treated with NaCl solution (left). Many mitotic figures are seen in the tumor from the non-treated animal compared to the tumor from the treated animal. Pictures were taken at an original magnification of 400×.

Mentions: In the second series of experiments (Fig. 2b) the animals were not treated with anhydrotetracycline. Instead, the animals were sacrificed and the tumours removed in order to analyse mitotic activity. Paraffin imbedded sections were analysed as described in the Materials and Methods section. Microscopy revealed that all tumors showed a highly malignant mostly sarcoma-like morphology. Compared to the tumours from non-treated animals, the nuclei of carnosine treated tumours were less pleomorph (Fig. 3). Most interestingly, the tumours in the carnosine treated group exhibited a significantly lower number of mitoses per high power field (14.0 ± 1.58 mitoses/HPF) compared to the tumors from control mice (21.6 ± 2.19 mitoses/HPF; P < 0.0003).


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

Renner C, Zemitzsch N, Fuchs B, Geiger KD, Hermes M, Hengstler J, Gebhardt R, Meixensberger J, Gaunitz F - Mol. Cancer (2010)

Microscopic images from tumors stained with Hematoxylin-Eosin from an animal treated with carnosine (right) and from a control animal treated with NaCl solution (left). Many mitotic figures are seen in the tumor from the non-treated animal compared to the tumor from the treated animal. Pictures were taken at an original magnification of 400×.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2818694&req=5

Figure 3: Microscopic images from tumors stained with Hematoxylin-Eosin from an animal treated with carnosine (right) and from a control animal treated with NaCl solution (left). Many mitotic figures are seen in the tumor from the non-treated animal compared to the tumor from the treated animal. Pictures were taken at an original magnification of 400×.
Mentions: In the second series of experiments (Fig. 2b) the animals were not treated with anhydrotetracycline. Instead, the animals were sacrificed and the tumours removed in order to analyse mitotic activity. Paraffin imbedded sections were analysed as described in the Materials and Methods section. Microscopy revealed that all tumors showed a highly malignant mostly sarcoma-like morphology. Compared to the tumours from non-treated animals, the nuclei of carnosine treated tumours were less pleomorph (Fig. 3). Most interestingly, the tumours in the carnosine treated group exhibited a significantly lower number of mitoses per high power field (14.0 ± 1.58 mitoses/HPF) compared to the tumors from control mice (21.6 ± 2.19 mitoses/HPF; P < 0.0003).

Bottom Line: A significant effect of carnosine on tumor growth was observed up to day 24.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Leipzig und Medizinische Fakultät der Universität Leipzig, Leipzig, Germany.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus